Para médicos · reumatologia
Resumos de artigos, podcasts e newsletters sobre Síndrome de Sjögren, para atualização médica.
A newsletter discute como a obesidade atenua a resposta aos inibidores de JAK na artrite reumatoide, enfatizando que o IMC elevado é um modificador de efeito clínico relevante. O conteúdo também aborda a alta prevalência de critérios de fibromialgia em pacientes pós-COVID, a conduta expectante na artrite por parvovírus B19 e a associação genética entre regulação tireoidiana e deposição de cristais de pirofosfato de cálcio.
A newsletter discute a descoberta de que a assinatura do interferon tipo 1 pode preceder o diagnóstico da Síndrome de Sjögren em até 14 anos, definindo um endotipo biológico específico. Além disso, aborda o aumento da detecção de miopatias necrosantes por estatinas e a integração de mecanismos inflamatórios na perda de massa óssea e muscular em pacientes obesos.
A newsletter discute a alta prevalência de manifestações cardíacas na Síndrome de Behçet, frequentemente subestimada e associada à atividade sistêmica da doença. O conteúdo também aborda a importância do rastreio de HPV em pacientes imunossuprimidos e apresenta a LBFSS, a primeira escala específica para mensurar a disfunção cognitiva no Lúpus.
To co-develop disease-specific patient questions for connective tissue diseases (CTDs), compare patient/rheumatologist ratings of answers from language models (LLMs) versus Google Search, and quantify EULAR coverage of these patient-prioritized questions. In this prospective single-center observational study, reported in accordance with STROBE, patient advocacy groups curated 20 frequently asked questions (FAQs) for each CTD (systemic lupus erythematosus, idiopathic inflammatory myopathy, Sjögren disease, systemic sclerosis). Questions were submitted to Claude 4.0 Sonnet, ChatGPT-5, Gemini 2.5 Pro, and Google Search. Five patients per disease and five rheumatologists rated blinded outputs using forced-rank preference and 5-point Likert scales (patients: empathy, trustworthiness, comprehensibility; physicians: medical correctness, empathy, comprehensibility). Guideline mapping assessed whether EULAR recommendations addressed each question. All three LLMs answered 100% of questions (80/80), whereas Google Search answered 90% (72/80). Across CTDs, patients rated LLM outputs favorably for empathy (mean 1.40-2.77), trustworthiness (1.47-2.6), and comprehensibility (1.33-2.27), and rheumatologists for medical correctness (1.23-1.98). Patients and physicians most often ranked Gemini 2.5 Pro best overall (rank 1: 59% and 63%), and Google Search most often worst (rank 4: 55% and 57%). Cluster analyses showed no consistent differences across five clusters. Guideline mapping revealed substantial gaps: 40-55% of prioritized FAQs were not addressed by EULAR recommendations, with largest gaps in cluster E, life impact, psychosocial aspects and family planning (75-100% not addressed; 0% fully addressed). In this blinded evaluation, LLMs produced CTD FAQs responses patients perceived as empathic, trustworthy and rheumatologists rated medically correct, with Gemini 2.5 Pro most consistently preferred overall. However, the mismatch between prioritized questions and guideline coverage underscores the need for patient-centered, evidence-grounded information resources.
A newsletter destaca os avanços do EULAR 2026, com ênfase no estudo INDIGO sobre o obexelimabe na doença relacionada à IgG4 e no papel do metotrexato na redução da progressão para artrite reumatoide em pacientes ACPA-negativos. Além disso, discute a importância da padronização na fisioterapia para osteoartrite e o uso combinado de biomarcadores e ultrassom para triagem de doença pulmonar intersticial.
OBJECTIVES: To assess the long-term outcomes and prognostic factors of patients presenting with all-cause mixed cryoglobulinemia vasculitis (CryoVas). METHODS: A European multicentre cohort study (EuroCryo) of 1,294 patients presenting with all-cause CryoVas. RESULTS: The main aetiology for CryoVas was HCV with 469 (36%) cases, followed by essential forms (n = 344, 26%) and autoimmune conditions (n = 302, 23%) with Sjogren's disease being the most common (n = 268, 21%). Over a median follow-up of 2.8 years, a total of 558 CryoVas patients experienced 661 severe events, notably 221 relapses, 52 severe infections and 45 lymphomas. Multivariable model for event-free survival retained a post-2014 diagnosis, male sex, older age, low C4 levels, positive rheumatoid factor and higher baseline creatinine levels as poor prognostic factors; HCV aetiology was protective. Factors associated with the occurrence of lymphoma were a post-2014 diagnosis, autoimmune aetiology, fever, fatigue and low C4 levels. CONCLUSION: HCV was for long considered a poor prognosis factor in CryoVas, and now those secondary to autoimmune conditions seem to evolve with a more severe course, notably carrying a higher lymphoma risk.
Incomplete lupus erythematosus (ILE) and non-Sjögren’s disease sicca (nSjD-sicca) are clinically heterogeneous, incompletely classified autoimmune conditions that share features with systemic lupus erythematosus (SLE) and Sjögren’s disease (SjD), respectively. Although some patients progress to classified disease, many remain stable. The immunologic features distinguishing incomplete from established autoimmune disease remain poorly defined. We sought to characterize and compare autoantibody immune signatures across ILE, SLE, nSjD-sicca, and SjD using expanded autoantibody profiling. Serum samples were obtained from patients with ILE (n=80), SLE (n=80), nSjD-sicca (n=52), SjD (n=60), and matched healthy controls (n=79). Initial screening was performed using the Bio-Rad BioPlex 2200. Expanded profiling utilized the GeneCopoeia Human Autoimmune Array (120 autoantigens) with parallel IgM and IgG detection. Traditional screening demonstrated expected patterns: ILE (anti-nRNP 26.3%; anti-chromatin 25.0%), SLE (anti-SmRNP 40.0%; anti-dsDNA 31.3%), nSjD-sicca (anti-La 9.6%), and SjD (anti-Ro/SSA 53.3%). Expanded analysis revealed significantly increased IgM autoreactivity in ILE compared with SLE (BH-FDR-adjusted p<0.05), targeting nuclear (KU, Nup62, CENP-A/B), cytokine (IFN-α1, IFN-ϵ, IL-15, GM-CSF), mitochondrial (M2), extracellular matrix (collagen IV, fibrinogen), vascular (β2-glycoprotein I, AGTR), and gut-associated antigens (tissue transglutaminase, intrinsic factor). In contrast, SLE demonstrated enriched IgG responses to canonical nuclear antigens, including core histone and dsDNA. Within the sicca spectrum, Ro52 (TRIM21) IgG autoantibodies were significantly increased in SjD compared to nSjD-sicca. These findings indicate that incomplete autoimmune disease states exhibit distinct IgM-dominant autoantibody profiles rather than simply attenuated versions of the IgG dominant responses in classified disease, highlighting the potential value of isotype-specific profiling for disease classification.
Objectives To evaluate the clinical characteristics of leukopenia in hospitalized patients with Sjögren’s disease (SjD), particularly its association with systemic organ involvement, immunological activity, and disease duration. Methods This retrospective exploratory study of 200 hospitalized patients with SjD admitted to a tertiary medical center between 2017 and 2023. Patients were divided into leukopenia and normal white blood cell (WBC) groups according to WBC count. Demographic characteristics, hematologic parameters, inflammatory and immunological markers, and systemic organ involvement were compared between groups. Among patients with leukopenia, disease duration was further stratified into tertiles to explore duration-related patterns. Where data are available, multivariable logistic regression should be performed to explore whether leukopenia is associated with selected systemic manifestations after adjustment for disease duration and treatment exposure. Results Leukopenia occurred in 67 of 200 patients (33.5%). Compared with patients with normal WBC counts, patients with leukopenia had lower hemoglobin and platelet counts. The proportions of interstitial lung disease (ILD), pulmonary hypertension/suspected pulmonary arterial hypertension, peripheral nervous system involvement, and skin, joint, and muscle involvement were not significantly different between the leukopenia and normal WBC groups. In the leukopenia group, however, the prevalence of ILD increased across disease-duration quartiles, from 14.8% in Q1 (≤ 3 years) to 40.7% in Q4 (> 11 years). IgG and erythrocyte sedimentation rate were higher in early-duration leukopenic patients and lower in later-duration strata, suggesting a possible change in inflammatory activity rather than proven immune exhaustion. Conclusions In this hospitalized SjD cohort, leukopenia was a common hematologic abnormality but was not significantly associated with most systemic manifestations in direct between-group comparisons. Within the leukopenic subgroup, a higher prevalence of ILD was observed across longer disease-duration strata, a hypothesis-generating finding rather than evidence
A newsletter apresenta os principais destaques do congresso EULAR 2026, abordando desde a eficácia da manutenção do alopurinol na gota até novos alvos terapêuticos para a Síndrome de Sjögren. Além das atualizações clínicas, explora como fatores psicossociais e a satisfação conjugal influenciam diretamente o prognóstico e a saúde mental de pacientes com doenças reumáticas crônicas.
Background Sjögren disease (SjD) is an autoimmune disorder marked by exocrine gland dysfunction and systemic extraglandular manifestations (EGM). While nutritional status plays a key role in chronic diseases, its association with EGM in SjD remains underexplored. Aims This study aims to evaluate the nutritional status of patients with SjD using two validated tools the Controlling Nutritional Status (CONUT) score and the Prognostic Nutritional Index (PNI) and to examine their relationship with EGM. Methods A cross-sectional analysis was conducted on 113 patients diagnosed with SjD, categorized into two groups: those with EGM (n = 26) and those without (n = 87). Nutritional status was assessed using serum albumin, total lymphocyte count, and total cholesterol for CONUT, and serum albumin with lymphocyte count for PNI. Clinical, serological, and laboratory data were collected, including the EULAR Sjögren’s Syndrome Disease Activity Index (ESSDAI). Results The mean age of participants was 56.2 ± 10.9 years, with 94.7% being female. The EGM group exhibited a significantly higher prevalence of anti-Ro and anti-Ro-52 antibodies. Compared to the non-EGM group, the EGM group had significantly lower levels of albumin, white blood cells, neutrophils, lymphocytes, and PNI scores, and higher ESSDAI and CONUT scores. Multivariate logistic regression identified ESSDAI, CONUT and PNI scores were independently associated with the presence of EGM at diagnosis. Conclusion This study underscores the importance of nutritional assessment in SjD, particularly in patients with systemic involvement. Malnutrition, as reflected by CONUT and PNI, is significantly associated with the presence of EGM. These findings highlight the need for routine nutritional screening in SjD management to support comprehensive care and improve patient outcomes.
Objective Individuals with systemic autoimmune rheumatic diseases (SARDs) are at risk for worse acute and post–acute COVID‐19 outcomes, though whether individuals with SARDs have longer persistence of viral antigens after COVID‐19 has not been studied. Methods This retrospective cohort study evaluated post–COVID‐19 differences in SARS‐CoV‐2 antigen (spike, spike protein that contains the receptor‐binding domain, and nucleocapsid) positivity between individuals with SARDs (COVID‐19 and Rheumatic Diseases [RheumCARD]) and without SARDs (Researching COVID to Enhance Recovery [RECOVER]–Adult). SARS‐CoV‐2 antigens were measured in collected samples using a validated ultrasensitive single molecule array. This digital enzyme‐linked immunosorbent assay used antibody‐coated magnetic beads to capture antigen molecules, which were loaded into microwell arrays and detected through enzymatic cleavage of a fluorescent substrate. We used logistic regression to estimate unadjusted and adjusted (for age, sex, infection year, vaccination status, and COVID‐19 treatment) odds ratios for SARS‐CoV‐2 antigen positivity at months 3 and 6 following COVID‐19. Results Among 210 individuals with SARDs in RheumCARD and 348 individuals without SARDs in RECOVER‐Adult, any SARS‐CoV‐2 antigen positivity was more common in those with SARDs (36.7% in RheumCARD vs 18.9% in RECOVER‐Adult; P < 0.001). Those with SARDs had higher odds of nucleocapsid antigen positivity (adjusted odds ratio [aOR] 3.73, 95% confidence interval [CI] 1.28–10.85) or any antigen positivity (aOR 2.89, 95% CI 1.43–5.85) three months after COVID‐19 infection and higher odds of nucleocapsid antigen positivity (aOR 6.62, 95% CI 1.09–40.30) six months after COVID‐19 infection. Conclusion Individuals with SARDs were more likely to have SARS‐CoV‐2 antigen positivity at months 3 and 6 following COVID‐19 infection compared with individuals without SARDs, not explained by demographics, variant, vaccination, or treatment.
A newsletter destaca os resultados do estudo de fase 3 VALOR, que comprovou a eficácia do brepocitinibe na melhora cutânea e muscular da dermatomiosite, permitindo o desmame de corticoides. São discutidas também inovações como o uso de blinatumomabe para restaurar a responsividade terapêutica na artrite reumatoide e a aplicação de células CAR-T em casos refratários, além de novos escores para estratificação de risco gestacional.
A newsletter discute os desafios práticos e emocionais da maternidade em mulheres com doenças reumáticas, destacando que o cuidado médico deve transcender métricas clínicas como o DAS-28. Além disso, apresenta atualizações científicas sobre novos biomarcadores de inflamação coronariana na artrite reumatoide e a caracterização de fenótipos específicos em pacientes com anticorpos anti-CENP-B e anti-SSA.
Isolated anti-SSB positivity is associated with a significantly lower likelihood of Sjögren disease, SLE, and RA. These findings suggest that isolated anti-SSB may lack diagnostic utility and could represent a clinically insignificant serologic finding in many patients.
Background Sjögren’s disease (SjD) is a chronic systemic autoimmune disorder characterized by glandular dysfunction and variable extraglandular organ involvement. Although the disease predominantly affects women, the clinical expression of SjD may differ between genders. Objectives To evaluate gender-associated differences in glandular and extraglandular manifestations, systemic disease activity, and the predictive performance of serological markers for high disease activity in patients with SjD. Methods This retrospective cohort study included patients fulfilling the 2016 ACR/EULAR classification criteria for SjD who were followed at a tertiary rheumatology center. Demographic characteristics, glandular manifestations, extraglandular organ involvement, laboratory findings, and systemic disease activity assessed using the EULAR Sjögren’s Syndrome Disease Activity Index (ESSDAI) were recorded. High disease activity was defined as ESSDAI ≥ 5. Gender-stratified comparisons were performed, and receiver operating characteristic (ROC) analyses were conducted to evaluate the ability of serological markers to discriminate high disease activity. Results A total of 191 patients were included (117 women and 74 men). Female patients more frequently presented with glandular symptoms, including xerostomia and xerophthalmia, as well as musculoskeletal manifestations such as arthralgia. In contrast, male patients exhibited a higher frequency of pulmonary involvement. Although mean ESSDAI scores were higher in men, multivariable logistic regression analyses adjusting for age, disease duration, and smoking status indicated that gender was not independently associated with high systemic disease activity. Instead, pulmonary involvement emerged as the strongest predictor of elevated ESSDAI scores. ROC analyses demonstrated limited discriminatory ability of conventional serological markers for identifying patients with high disease activity. Conclusions In this cohort of patients with Sjögren’s disease, differences in systemic disease activity between genders appeared to be primarily related to patterns of organ involvement rather than gender itself. Pulmonary manifestations
Objective Sjögren disease (SjD) is characterized by autoimmune lymphocytic infiltration of lacrimal and salivary glands, leading to dry eye and dry mouth. This study aimed to investigate the features and diagnostic value of lacrimal gland ultrasonography (LGUS) for distinguishing SjD from undifferentiated connective tissue diseases (UCTDs). Methods This prospective cohort study enrolled 80 patients, including 46 with SjD and 34 with non-SjD UCTDs. All participants underwent LGUS, scored according to the OMERACT guidelines for greyscale and color Doppler systems, alongside salivary gland ultrasonography (SGUS) and objective dry eye tests. Diagnostic performance was assessed using receiver operating characteristic (ROC) analysis. Results The ocular surface evaluation including tear break-up time (BUT), Schirmer test (ST), ocular staining score (OSS), and LGUS greyscale score of patients with SjD showed significant differences as compared with non-SjD patients, while no difference was found in morphology and color Doppler ultrasound score between the two groups. The ROC of LGUS has an AUC of 0.70 (95% CI 0.579–0.810) compared to other CTD patients; the combined LGUS and SGUS model achieved an AUC of 0.76, while a multivariate nomogram incorporating LGUS, SGUS, Schirmer, and OSS yielded an AUC of 0.792 (95% CI 0.693–0.891). Besides, a significant correlation was found between the LGUS greyscale score and salivary gland involved, anti-SSA antibody, and the ocular surface parameters. Conclusion LGUS is a non-invasive, cost-effective adjunct for early SjD diagnosis. It can be an additional tool integrated with SGUS and clinical tests, substantially improving diagnostic performance. Key Points • SjD patients showed significantly higher LGUS greyscale score than non-SjD UCTD patients. • LGUS may aid early SjD identification when used alongside ocular surface tests (Schirmer test and ocular staining score), with high specificity
Abstract OBJECTIVES In a cross-sectional study, we aimed at characterizing possible impairments in sleep health and rest–activity parameters between patients with Sjögren’s Disease (SjD) and healthy controls (HCs). Furthermore, we explored possible predictors of such disturbances in the SjD group. METHODS Participants’ sleep and rest-activity rhythms were assessed via 7-day continuous accelerometry, the Pittsburgh Sleep Quality Index, the Epworth Sleepiness Scale, and the reduced Morningness-Eveningness Questionnaire, allowing the creation of a multidimensional sleep health index. Parametric tests explored between-group differences in sleep and rest-activity parameters, while functional linear modelling characterized between-group, time-related differences in accelerometric activity. Within the SjD cohort, regression analysis was employed to explore disease activity, patient-reported disease burden, and the Hospital Anxiety and Depression Scale (HADS) as possible predictors of sleep and rest-activity parameters. RESULTS Forty-six SjD patients and forty age-, sex- and BMI-matched HCs were included. Compared with HCs, SjD patients reported lower sleep health (p= 0.005) and delayed mid-sleep point (p= 0.009) and acrophase (p= 0.033). Functional linear modelling confirmed the objective shift towards eveningness in SjD patients. In SjD patients, patient-reported disease burden predicted sleep quality (β = 0.41; p= 0.044) and sleepiness (β = 0.83; p= 0.010), while disease activity predicted daily steps (β=-526; p= 0.013), total sleep time (β = 0.15; p= 0.0496) and sleep regularity (β=-1.3; p= 0.030). Finally, HADS predicted daily steps (β=-238; p= 0.041), total sleep time (β=-0.08; p= 0.035) and sleep efficiency (β=-0.65; p= 0.012). CONCLUSIONS SjD is associated with impaired sleep health and rest-activity rhythms. In SjD patients, such alterations differentially associate with disease activity and patient-reported outcomes, supporting a multifactorial model of sleep and circadian rhythms disruption.
Anti-SS-A (Ro) antibody-positive rheumatoid arthritis (RA) constitutes a clinically important subgroup, but its impact on retention of biologic or targeted synthetic disease-modifying antirheumatic drugs (b/tsDMARDs) across different modes of action (MOA) and reasons for discontinuation remains unclear. We conducted a multicenter retrospective analysis of the Japanese ANSWER cohort, including RA patients who started or switched b/tsDMARDs between 2011 and 2024 and had baseline anti-SS-A antibody testing. Among 1,452 patients (2,703 treatment courses), 255 patients (17.6%) were anti-SS-A antibody positive (507 courses, 18.8%). Propensity score matching balanced baseline characteristics, and drug retention was evaluated using Kaplan-Meier and competing risk analyses. Overall discontinuation was analyzed using Cox proportional hazards models, and Fine-Gray subdistribution hazards models were used for discontinuation by reason and for adverse event-related discontinuation stratified by MOA. After matching, 507 treatment courses from 255 anti-SS-A antibody-positive patients and 1,014 courses from 628 antibody-negative patients were analyzed. Anti-SS-A antibody positivity was not associated with overall b/tsDMARD retention (hazard ratio [HR] 1.07, 95% confidence interval [CI] 0.91-1.26, p = 0.382). In MOA-stratified analyses, positivity showed a trend toward increased discontinuation with interleukin-6 (IL-6) receptor inhibitors and cytotoxic T lymphocyte-associated antigen 4-immunoglobulin (CTLA4-Ig). In competing-risk analyses, discontinuation due to adverse events was significantly more frequent in antibody-positive patients (subdistribution hazard ratio [sHR] 1.80, 95% CI 1.28-2.52; p = 0.000685). Among adverse event-related discontinuations, anti-SS-A antibody positivity was associated with higher risks with IL-6 receptor inhibitors (sHR 2.41, 95% CI 1.24-4.71; p = 0.0098) and tumor necrosis factor (TNF) inhibitors (sHR 2.04, 95% CI 1.22-3.40; p = 0.0066), but not with CTLA4-Ig or Janus kinase (JAK) inhibitors. These findings suggest that treatment tolerability, rather than overall efficacy, may be a key determinant of b/tsDMARD
Arthritis &amp;Rheumatology, Volume 78, Issue 3, Page 558-565, March 2026.
A newsletter destaca a importância do anticorpo anti-nucleossomo como marcador complementar no lúpus, especialmente para manifestações neuropsiquiátricas e renais onde o anti-dsDNA pode ser negativo. Além disso, aborda a segurança dos DMARDs na artrite reumatoide com doença pulmonar intersticial, indicando que biológicos não-TNF podem estar associados a um maior risco de hospitalização por pneumonia.
A newsletter analisa uma meta-análise que indica benefícios significativos da metformina na redução da dor e melhora funcional em pacientes com osteoartrite de joelho. Outro destaque é a discussão sobre o mimetismo clínico entre a artrite reumatoide soronegativa e a doença por depósito de pirofosfato de cálcio (CPPD), especialmente em pacientes idosos. O conteúdo também revisa os principais avanços terapêuticos de 2025 em doenças como lúpus, esclerose sistêmica e IgG4-RD.
High-resolution, high-throughput single-cell omics has transformed our understanding of autoimmune disease pathogenesis. We synthesise recent single-cell omics advances across six autoimmune diseases-systemic sclerosis, systemic lupus erythematosus, Sjögren's syndrome, ankylosing spondylitis, IgG4-related disease and rheumatoid arthritis. We further summarise translational progress in targeted therapies. We delineate core pathological networks shared across these conditions, highlight convergent mechanisms, and provide a mechanistic rationale for the clinical activity of agents such as tofacitinib and abatacept across multiple autoimmune settings. These insights support the feasibility of mechanism-informed, cross-disease targeting-deploying shared pathway interventions across distinct clinical entities. Finally, we discuss current technical and interpretative challenges and outline future directions for mechanistic discovery, target prioritisation and precision medicine.
Although immune checkpoint inhibitors (ICIs) have improved survival in head and neck squamous cell carcinoma (HNSCC), associated adverse events, such as sialadenitis, remain poorly characterized. This study aimed to define the clinicopathological features, establish the causal pathogenic mechanism, and validate a therapeutic target for ICI-associated sialadenitis. This study integrated three complementary approaches. First, a prospective cohort of 25 HNSCC patients underwent functional assessment of salivary and lacrimal glands before and after ICI therapy. Second, salivary gland tissues from separate cohorts of ICI-treated (n=30) and untreated control (n=30) patients were subjected to comprehensive analysis, including histology, multi-platform immunophenotyping (immunohistochemistry, multiplex immunofluorescence, flow cytometry), and cytokine quantification at both transcript and protein levels. Finally, a preclinical mouse model was established to confirm causality and validate the therapeutic efficacy of IL-17A blockade. Following ICI treatment, patients showed significantly reduced salivary and lacrimal secretion (P < 0.05). Histopathological analysis revealed extensive lymphocytic infiltration, marked periductal fibrosis, and substantial loss of acinar structures. The immune infiltrate was dominated by CD4+ T cells, particularly the Th17 subset, with corresponding upregulation of IL-17A both at transcriptional and protein levels. Crucially, we established a mouse model of anti-PD-1-induced sialadenitis and demonstrated that therapeutic blockade of IL-17A restores salivary function. This study establishes ICI-associated sialadenitis as a distinct pathological entity characterized by CD4+T cell-driven inflammation mediated through the Th17/IL-17 axis, which differs from Sjögren syndrome, predominantly involving B cells and from IgG4 related sialadenitis. By demonstrating therapeutic efficacy in a preclinical model, our findings provide the first preclinical validation of the IL-17 axis as an actionable therapeutic target for this condition.
While Sjögren disease (SjD) overlap is known to modulate the clinical-serologic manifestations of other connective tissue diseases, the association with anti-synthetase syndrome (ASyS) has been seldom described in Caucasian cohorts. Anti-Ro52 autoantibodies, shared by both conditions, may blur early diagnostic attribution, particularly when glandular symptoms precede myositis-spectrum features. To characterize the clinical phenotype, serological profile, and disease trajectory of patients fulfilling classification criteria for both SjD and ASyS. We conducted a multicentre retrospective study (2018-2025) across three Italian referral centres, including patients meeting both the 2016 ACR/EULAR SjD criteria and the Connor's/provisional CLASS classification criteria for ASyS. Clinical features, serology, interstitial lung disease (ILD) characteristics, treatments, and outcomes were systematically collected. SjD activity was assessed using the ESSDAI and an adapted ESSDAI excluding the classic ASyS triad (pulmonary, articular and muscular domains). Seventeen female patients of Caucasian ethnicity were identified. At the time of connective tissue disease diagnosis, 7 were classified as SjD and 10 received concomitant diagnoses; all reported early sicca symptoms. Regarding serology, anti-Ro52 antibodies were detected in all patients, most often (88%) in the absence of anti-Ro60 antibodies. Anti-synthetase antibodies were present in all cases, mainly non-Jo-1 specificities (77%), while anti-Jo-1 was observed in a minority of patients (23%). ILD was the leading organ involvement (14/17, 82%), typically with acute/subacute onset and NSIP or NSIP/OP patterns. ILD drove treatment decisions and accounted for four deaths, whereas most survivors showed stabilization or mild improvement under immunosuppressive treatment. Systemic assessment indicated a predominantly ASyS-driven phenotype: although ESSDAI was moderately elevated (median 15, IQR 7.5-21), the adapted ESSDAI markedly decreased (median 5, IQR 0-6.5), reflecting limited SjD-specific systemic activity. The SjD-ASyS overlap seem characterized by a coherent clinical-serological phenotype, defined
This study aimed to identify interferon (IFN)-related key genes in patients with Sjögren's Disease (SjD) and to elucidate their specific associations with the heterogeneous clinical phenotypes and laboratory parameters of the disease. Bioinformatics analyses, including differentially expressed gene (DEG) screening, weighted gene co-expression network analysis (WGCNA), and machine learning, were conducted on dataset GSE84844 to identify IFN-related key genes. Based on the EULAR Sjögren's syndrome disease activity index (ESSDAI), SjD patients with low, moderate, and high disease activity were enrolled, with 20 in each subgroup. Quantitative real-time polymerase chain reaction (qRT-PCR) was performed on peripheral blood mononuclear cells (PBMCs) from the 60 SjD patients and 15 healthy controls (HCs). Expression levels were compared between SjD patients and HCs, across disease activity subgroups, and correlated with clinical phenotypes and laboratory indicators. DEGs in SjD were significantly enriched in IFN-related signaling pathways. Five IFN-related hub genes were identified: CXCL10, DDX60L, IFIH1, JAK2, and NMI. qRT-PCR validation confirmed that all five genes were significantly upregulated in SjD patients compared to HCs (P < 0.05). However, their expression did not significantly differ among SjD subgroups with varying levels of overall disease activity (P > 0.05). Importantly, these genes were differentially expressed in distinct clinical manifestations. For instance, elevated CXCL10 expression was observed in patients with interstitial lung disease (ILD), leukopenia, and anemia; JAK2 expression differed in rheumatoid arthritis comorbidity; IFIH1 expression also showed differences in those with Raynaud's phenomenon and ILD. Furthermore, certain genes were highly expressed in specific laboratory abnormalities: elevated erythrocyte sedimentation rate with CXCL10 and JAK2; hyperglobulinemia with CXCL10, DDX60L, IFIH1, and JAK2; and elevated immunoglobulin G with CXCL10, DDX60L, and IFIH1 (all P < 0.05). This study identifies five IFN-related
Sjögren's disease (SjD) is a chronic autoimmune disorder characterized by dry mouth (xerostomia) and dry eyes (xerophthalmia) due to inflammation in exocrine glands, particularly the salivary and lacrimal glands. The condition presents a wide variety of clinical features, suggesting that it may involve heterogeneous conditions without a clear boundary. Although genome-wide association studies (GWAS) have identified several genetic variants associated with SjD, their roles in SjD pathogenesis remain unclear. In this study, we aimed to identify single-nucleotide polymorphisms (SNPs) associated with SjD by categorizing patients based on four diagnostic markers: anti-Ro/SSA and anti-La/SSB antibodies, IgG levels, and lymphocyte foci, using a genotype-phenotype dataset (NCBI dbGaP phs000672.v1.p1) which included 594 SjD patients, 1,264 sicca symptomatic individuals without SjD diagnosis (as a control group), and 41 healthy individuals (as another control group) . We identified SNPs associated with each subtype of SjD, organized by two factors of diagnostic markers, X (anti-SSA and/or anti-SSB autoantibody) and Y (IgG or lymphocyte foci), with an adjusted p-value less than 5x10-8. The SjD subtypes were classified as follows: Group A (Factors X+ and Y+), Group B (X+ and Y-), Group C (X- and Y+), and Group D (X- and Y-). We found distinct SNPs associated with each group of SjD patients. This study can help advance the SjD subtype investigation, supporting precision diagnosis and treatment of SjD.
The frequency of extractable nuclear antigen (ENA) seropositivity in patients with negative antinuclear antibodies (ANA) by indirect immunofluorescence (IIF) remains insufficiently characterized. We aimed to estimate the frequency of ENA seropositivity among ANA-IIF-negative individuals (ENA+/IIF-), and to identify associated clinical and methodological determinants. A systematic search of PubMed, EMBASE, Web of Science, and Scopus was conducted for studies published up to January 31, 2025. Studies evaluating ENA seropositivity in ANA-IIF-negative patients using HEp-2 or HEp-2000 substrates were included. Meta-analysis was performed using the Freeman-Tukey double arcsine transformation and random-effects models. Twenty-eight studies, comprising 33 distinct patient groups and 28,552 ANA-IIF-negative samples, were included. The pooled proportion of ENA+/IIF- was 14.1% (95% CI: 10%-18.7%), with substantial heterogeneity (I² = 99%). Subgroup analysis demonstrated significant variation according to clinical indication: 1.4% (95% CI: 1.1%-1.9%) in unspecified indications, 8.1% (95% CI: 6%-10.5%) in suspected connective tissue disease (CTD), and 44.1% (95% CI: 32.3%-54.6%) in confirmed CTD (p < 0.0001). Multivariable meta-regression identified the IIF cut-off dilution, anti-SSA/Ro antibodies, and anti-tRNA synthetase antibodies as significant determinants of ENA+/IIF- frequency. This meta-analysis confirmed that ENA seropositivity is not uncommon in ANA-IIF-negative individuals, and it varies according to clinical context. A negative ANA-IIF result does not reliably exclude CTD, particularly in patients with strong clinical suspicion of CTD. These findings support a targeted, clinically driven ENA testing strategy, especially in conditions such as Sjögren syndrome and inflammatory myopathies. https://www.crd.york.ac.uk/PROSPERO/view/, identifier CRD420250654499.
Stem cell therapy holds considerable potential for treating dry eye syndrome, though it has yet to receive clinical approval. This paper systematically quantifies the efficacy and safety of stem cell-based therapies in dry eye syndrome caused by Sjögren's syndrome, aiming to provide information for dry eye treatment efforts. This systematic review collected literature published prior to 16 January 2026 in PubMed, Embase, and the Cochrane Library concerning stem cell therapy for Sjögren's syndrome-induced dry eye disease. Efficacy outcomes comprised: OSDI scores, along with changes in NIKBUT first, Oxford score, and Schirmer test results. Safety outcomes comprised commonly reported adverse events. Continuous outcomes were expressed as mean difference (MD), while dichotomous outcomes used single-group rates, both presented with 95% CI. All data analyses were conducted using Review Manager 5.4 software, adhering to the PRISMA guidelines. This meta-analysis included five studies involving 114 patients with dry eye syndrome. Results demonstrated that stem cell therapy significantly altered the OSDI score compared to pre-treatment levels: -15.10 (95% CI: -18.65, -11.56; P < 0.00001). NIKBUT first scores increased significantly by 3.26 points post-treatment (95% CI: 2.17, 4.34; P < 0.00001). The Oxford score showed a change of -0.20 (95% CI: -0.85, 0.45; P = 0.55) post-treatment. The Schirmer test score exhibited an overall change of 3.87 (95% CI: 1.93, 5.81; P < 0.0001). Specifically, the MD at 2 weeks, 4 months, and 12 months was 8.76 (95% CI: 0.58, 16.94; P < 0.04), 3.52 (95% CI: 1.66, 5.38; P < 0.002), and 5.10 (95% CI: 0.24, 9.96; P < 0.04), respectively. The incidence of injection pain at 4 weeks was 14% (95% CI: -11%, 39%, P = 0.28). Ocular discomfort occurred in 16% of subjects at 4 weeks (95%
Autoimmune diseases involve disruptions in immune tolerance, persistent systemic inflammation, and progressive multi-organ involvement, with increasing global prevalence. Accurate prediction of disease flares and complications, alongside tools for activity stratification, represents a significant clinical challenge. C-reactive protein (CRP), a canonical pattern recognition molecule of the pentraxin family, is a widely employed inflammatory biomarker; however, its expression patterns, cellular origins, and disease-specific roles across autoimmune conditions have not been comprehensively assessed. This study integrated retrospective clinical cohort analyses from Nanjing Drum Tower Hospital with population-level data from the National Health and Nutrition Examination Survey, proteomic profiling, and single-cell RNA sequencing to examine CRP expression across multiple autoimmune diseases, including systemic lupus erythematosus, Sjögren's disease, autoimmune hepatitis, and various inflammatory arthritides. Clinical data indicate that CRP levels exhibit considerable heterogeneity across these conditions. Proteomic analyses identify CRP as a core inflammatory mediator in conditions such as rheumatoid arthritis, while single-cell RNA sequencing delineates its major cellular sources. Integration of population-level data supports these heterogeneous patterns and demonstrates positive correlations between CRP levels and systemic inflammatory burden, as well as associations with hematologic parameters. Additionally, liver-derived single-cell and spatial transcriptomic data offer insights into the tissue-specific inflammatory landscape in autoimmune hepatitis. Collectively, this study maps the CRP expression landscape across multiple autoimmune diseases and identifies cellular sources in specific disease contexts. These findings indicate that CRP interpretation in autoimmune settings requires consideration of both disease type and clinical context, which may inform more refined strategies for early detection and patient stratification.
The CD40-CD40L axis is a central costimulatory pathway that links innate and adaptive immunity and contributes to autoimmune inflammation. However, CD40 signaling does not operate in the same way across cell types, and these differences are relevant to both therapeutic efficacy and safety. In this review, we discuss the molecular features of CD40 and CD40L, the TRAF-dependent signaling pathways activated downstream of CD40, and the distinct cellular responses observed in B cells, dendritic cells, and macrophages. We also examine how dysregulated CD40/CD40L signaling contributes to key pathological features of Rheumatoid arthritis, Systemic lupus erythematosus, and Sjögren's syndrome, including ectopic germinal center reactions, pathogenic autoantibody production, and chronic tissue inflammation. Platelet-derived CD40L and CD40 expression on vascular cells may also help explain the thromboembolic complications observed with early CD40/CD40L-targeted biologics. Current evidence suggests that safer therapeutic targeting of this pathway will require greater selectivity, particularly with respect to cell-specific signaling and Fc-mediated adverse effects.
Purpose of review CD40 ligand (CD40L, CD154) is a costimulatory molecule required for adaptive immune responses. It arms CD4 + T cells to provide critical “help” to B cells, dendritic cells, and other antigen-presenting cells through interactions with CD40. Enhanced CD40L signaling promotes autoreactive B cell activation, germinal center hyperactivity, and autoantibody production, processes central to autoimmune pathogenesis. Recognition of the pathway's importance in autoimmunity prompted clinical trials of anti-CD40L monoclonal antibodies in lupus, but early enthusiasm faded after unexpected thrombotic events. These first generation anti-CD40L antibodies were later found to trigger platelet activation through an Fc-mediated mechanism and led to re-engineering of antagonist therapeutic proteins. Recent findings Preclinical studies confirm that CD40L inhibition ameliorates disease across diverse autoimmune models by restraining aberrant B-cell and T-cell responses. Novel Fc-silent anti-CD40L antibodies, nonantibody CD40L antagonists, and anti-CD40 antibodies have since been developed to overcome prior safety concerns. These new-generation CD40L and CD40 antagonists have shown promising results in phase 2 trials spanning multiple autoimmune settings, renewing interest in therapeutic blockade of this pathway. Summary Next-generation CD40L and CD40-directed therapies are redefining costimulatory blockade in autoimmunity. Integrating preclinical discoveries with clinical translation offers new opportunities to optimize treatment and transform management of B cell-driven autoimmune disease.
A newsletter discute o impacto do belimumabe no lúpus inicial, demonstrando redução na progressão da doença e maior sucesso no desmame de corticoides. Apresenta também dados da coorte brasileira APS-Rio sobre SAF primária, destacando que metade das re-tromboses ocorre mesmo em faixa terapêutica de INR, além de abordar atualizações em Artrite Psoriásica, FRAX 2.0 e Doença relacionada à IgG4.
A newsletter destaca que a sequência terapêutica na osteoporose é crítica, revelando que o uso de teriparatida após romosozumabe pode resultar em perda de força óssea estrutural. Além disso, fornece uma revisão detalhada sobre a sarcoidose extrapulmonar, enfatizando a importância da triagem cardíaca e ocular sistemática e o papel de exames avançados como PET-CT e RM cardíaca no manejo da doença.
A newsletter destaca como a aptidão cardiorrespiratória pode atenuar o declínio cognitivo e discute o potencial dos monócitos como marcadores acessíveis para doença pulmonar intersticial na artrite reumatoide. Além disso, correlaciona a inflamação intestinal à progressão radiográfica na espondiloartrite axial e analisa fatores que predizem a evolução da doença mista do tecido conjuntivo para outras patologias autoimunes.
A newsletter destaca o papel da inteligência artificial na redução da variabilidade diagnóstica da Síndrome de Sjögren e a caracterização de um subgrupo de progressão rápida na DISH associado a riscos metabólicos. Além disso, reforça que fatores metabólicos, e não o metotrexato, são os principais vilões da fibrose hepática na artrite psoriásica, e explora novas tecnologias para predição de flares e tratamentos intra-articulares.
A newsletter explora o papel emergente dos agonistas de GLP-1 na reumatologia, evidenciando melhorias em marcadores inflamatórios e desfechos clínicos, apesar da necessidade de estudos com maior robustez metodológica. Destaca-se também o uso da ultrassonografia para diferenciar fenótipos inflamatórios de quadros de sensibilização central na Artrite Psoriásica difícil de tratar, além de evidências que favorecem o uso de prednisona em relação à colchicina na artrite por pirofosfato de cálcio.
A newsletter destaca o papel do ultrassom como ferramenta diagnóstica robusta na Síndrome de Sjögren e na Polimialgia Reumática, além de apresentar resultados positivos de 104 semanas do upadacitinibe no tratamento do lúpus. O conteúdo também aborda a manometria esofágica como preditor de gravidade na esclerose sistêmica e a ineficácia da hidroxicloroquina em prevenir a progressão para artrite reumatoide clínica.
This study aimed to evaluate the prevalence of frailty and to identify its associated risk factors in hospitalized patients with Sjögren's disease (SjD). A cross-sectional study was conducted among hospitalized SjD patients at Xuanwu Hospital between August 2022 and October 2024. Frailty was evaluated using the Fried Frailty Phenotype, which comprises five components: unintentional weight loss, self-reported exhaustion, low physical activity, slowness, and weakness. Based on established criteria, patients were categorized as frail (≥3 criteria), pre-frail (1-2 criteria), or robust (0 criteria). A total of 180 patients were included in the final analysis. The prevalence of frailty and pre-frailty was 27% and 49%, respectively. Multivariate logistic regression analyses identified higher c-reactive protein (OR = 1.080, 95% CI: 1.020-1.144, P = 0.008), the EULAR Sjögren's Syndrome Disease Activity Index (OR = 1.082, 95% CI: 1.027-1.140, P = 0.003), and EULAR Sjögren's Syndrome Patient Reported Index (OR = 1.271, 95% CI: 1.064-1.518, P = 0.008) as independent risk factors for frailty. Frailty is commonly observed among hospitalized patients with SjD and is independently associated with systemic inflammation and disease activity. These findings underscore the need for routine frailty assessment in clinical practice, particularly among patients with elevated inflammatory markers and more severe disease manifestations.
IntroductionIndividuals with Sjögren's syndrome (SjD) experience notable health challenges, including chronic pain, fatigue, and depression; however, the potential benefits of physical activity in alleviating these issues remain unclear. We aim to systematically assess the comprehensive effects of physical activity on individuals with SjD.MethodsA comprehensive literature search was conducted in Medline, Embase, Scopus, Web of Science, Cochrane Library, SPORTDiscus, and ClinicalTrials.gov for studies published from inception to November 2025. Two independent reviewers screened the search results and extracted the data. Effect sizes were calculated as the standardized mean difference (SMDs) with 95% confidence intervals (CIs) using random-effects models. Methodological quality was assessed using the Cochrane Collaboration Risk of Bias Tool 2.0, and the certainty of evidence was evaluated with the GRADEpro online tool. Sensitivity, subgroup, and regression analyses were performed to explore potential sources of heterogeneity.ResultsThis analysis included six studies with a total of 277 participants with SjD. Compared to controls, physical activity interventions significantly improved cardiopulmonary function (SMD 0.59 [95% CI 0.20 to 0.99]), functional capacity (SMD 0.69 [95% CI 0.33 to 1.05]), general health status (SMD 0.46 [95% CI 0.15 to 0.76]), vitality (SMD 0.51 [95% CI 0.15 to 0.86]), and mental health (SMD 0.42 [95% CI 0.13 to 0.72]). However, no significant improvements were observed in pain, social aspects, fatigue, and the EULAR Sjögren's Syndrome Disease Activity Index.DiscussionThe results highlight aerobic and resistance training are regarded as effective and practical exercise options.Systematic Review Registrationhttps://www.crd.york.ac.uk/PROSPERO/, identifier CRD42024513141.
To examine national trends and disparities in cardiovascular mortality associated with systemic connective tissue disorders (CTDs) in the United States from 1999 to 2020. We analyzed mortality data from the CDC WONDER database. Deaths were included where CTD (ICD-10: M05, M06, M30-M35) was the underlying cause and cardiovascular disease was a contributing cause. Age-adjusted mortality rates (AAMRs) per 1 000 000 were calculated using the 2000 US Standard Population. Joinpoint regression identified annual and average annual percentage changes. Analyses were stratified by sex, race/ethnicity, census region, and urbanization. Disease subgroup and state-level analyses were performed. Between 1999 and 2020, 47 752 cardiovascular deaths occurred among individuals with systemic CTDs. The national AAMR declined from 14.4 to 8.2 per 1 000 000 (AAPC: -2.68%, 95% CI: -2.89 to -2.47, p < 0.001). Females had consistently higher mortality than males (average AAMR: 13.5 vs. 5.9 per 1 000 000; p < 0.001). Non-Hispanic Black individuals had the highest rates (average AAMR: 14.9 per 1 000 000), with widening disparities after 2008. Rural areas had higher mortality than urban areas (average AAMR: 11.4 vs. 9.9 per 1 000 000; p = 0.01). Subgroup analyses revealed heterogeneous trends across CTD subtypes, with SLE showing the slowest improvement (AAPC: -1.87%) and dermatomyositis the steepest decline (AAPC: -4.98%). State-level AAMRs ranged 2.2-fold, from 6.3 (District of Columbia) to 13.6 (Montana) per 1 000 000. Cardiovascular mortality associated with systemic CTDs has declined significantly over two decades; however, persistent racial disparities, urban-rural differences, heterogeneous disease-specific trends, and substantial geographic variation underscore the need for targeted, equitable interventions in this high-risk population.
To evaluate the diagnostic performance of BioPlex 2200 multiplex immunoassay (BI) for detecting antinuclear antibodies (ANA), compared with the gold standard, the indirect immunofluorescence assay (IIF), as a screening methodology for autoimmune diseases within a general population. Cross-sectional, database-based analysis of the Clalit Health Services nationwide registry. Data were extracted from the Clalit Health Services database between 2014 and 2023. We included adult outpatients without a known rheumatic disease who underwent both IIF and BI testing simultaneously, ordered for nonspecific signs and symptoms primarily by primary-care physicians. Among the 391,366 individuals tested, 67% were female, and the median age at testing was 49 years. Annual ANA testing volume increased from 23,802 in 2014 to 76,898 in 2023 (3.2-fold). Of the total, 33,234 (8.4%) tests were false negatives (BI-negative while IIF-positive), 42,021 (10.7%) were false positives (BI-positive while IIF-negative), 302,439 (77.2%) were true negatives, and 13,672 (3.5%) were true positives. BI demonstrated a sensitivity of 29.1% (95% CI: 28.7-29.6) and a specificity of 87.8% (95% CI: 87.7-87.9). The positive predictive value was 24.5% and the negative predictive value 90.1%. Our findings do not support the use of the BI multiplex immunoassay as a primary ANA screening tool in the primary-care setting. On the basis of these findings, the Clalit Health Services laboratory network discontinued simultaneous IIF and BI testing. The BI showed low sensitivity despite relatively high specificity, resulting in a substantial proportion of false-negative results compared with IIF. These findings indicate that it is not suitable as a primary screening tool for ANA in the primary-care setting.
To investigate whether structural integrity and epithelial senescence in the submandibular gland (SMG) predict longitudinal salivary gland dysfunction in Sjögren disease (SjD). This retrospective cohort study analysed 51 anti-SSA-positive SjD patients who underwent US-guided SMG core needle biopsy and longitudinal assessments of unstimulated whole saliva flow (UWSF). Glandular preservation was quantified as the SMG gland ratio (glandular area/total area), and epithelial senescence was assessed by p16INK4a expression in striated ductal epithelial cells. Associations with baseline and longitudinal UWSF were analysed using generalized estimating equations (GEEs). The SMG gland ratio correlated positively with baseline UWSF, serologic immunologic markers and imaging scores, supporting its role as a structural integrity index. However, patients with intermediate gland ratios experienced the steepest UWSF decline over time. Ductal p16 expression exhibited an inverted U-shaped distribution across the gland ratio spectrum, peaking at moderate preservation (ratio ≈ 0.55). In longitudinal models, higher p16 expression independently predicted greater UWSF decline (P < 0.001), whereas gland ratio alone was not significant. Patients with intermediate gland ratio and high p16 burden had the most rapid decline in salivary function. The SMG gland ratio reflects preserved glandular structure, while p16-mediated senescence captures functional vulnerability. Senescence peaks at an intermediate preservation stage, delineating a transitional disease phase in which function deteriorates despite intact architecture. These findings support a dual-pathology framework and may inform early risk stratification and therapeutic targeting in SjD.
Sjögren disease (SjD) is a systemic autoimmune disease characterized by increased risk of B-cell non-Hodgkin lymphoma. Although cryoglobulinemia and serum monoclonal component (MC) are well-recognized paraproteinemias in SjD, no large-scale study has directly compared their isolated and combined impact on phenotype and lymphoproliferative risk. A retrospective, multicenter, cross-sectional study was conducted within the Italian GRISS registry. Patients with SjD were stratified into four groups: isolated monoclonal gammopathy (MC-alone), isolated cryoglobulinemia (CRYO-alone), both (MC+CRYO), or neither (controls). Demographics, lymphoma history, ever-documented ClinESSDAI domains, and laboratory lymphoproliferative risk-related markers were analyzed. Primary and secondary outcomes assessed lymphoma diagnosis and the distribution of laboratory lymphoproliferative risk-related markers and ClinESSDAI domains across groups, with associations tested using logistic regression adjusted for confounders. 1202 SjD patients were enrolled: 58 (4.83%) in the MC-alone, 32 (2.66%) in the CRYO-alone, 35 (2.91%) in the MC+CRYO, and 1077 (89.60%) controls. Compared with controls, only the MC+CRYO group showed significant association with lymphoma (OR 6.30, 95%CI 2.66-14.92; p < 0.001), while MC-alone and CRYO-alone were not associated. Cryoglobulinemia, alone or combined with MC, correlated with laboratory lymphoproliferative risk-related markers such as rheumatoid factor (p < 0.001) and low C4 (p < 0.001), and with ClinESSDAI vasculitic features (cutaneous [p < 0.001], renal [p < 0.05], PNS [p < 0.001]). The MC+CRYO group additionally displayed a lymphoproliferative phenotype correlating with constitutional (p < 0.05), glandular (p < 0.05), hematological (p < 0.001), and lymphadenopathy (p < 0.001) domains. Cryoglobulinemia in SjD associates with vasculitic disease activity, whereas the coexistence of serum MC and cryoglobulins identifies a distinct, high-risk subset characterized by advanced B-cell expansion and increased lymphoma susceptibility.
Sjögren disease (SjD) is a common systemic autoimmune disease and patients experience a wide range of symptoms with unique emotional, social and physical impacts. Understanding the individual experience of SjD is crucial to providing comprehensive and sensitive care in the clinics. Therefore, the aim of this systematic review was to analyze primary literature that examined the lived experiences of patients with SjD. Primary literature qualitatively exploring the lived experiences of SjD patients through interviews and/or focus groups were identified. Papers were included if they were written in English, participants were ≥ 18 years old and they fulfilled a diagnosis of SjD as per the 2002 American-European Consensus or 2016 American College of Rheumatology/European Alliance of Associations for Rheumatology criteria. Thematic analyses were performed using the Thomas and Harden approach. Nine of 1990 screened manuscripts (0.5 %) fulfilled our selection criteria. These comprised a total of 162 participants (154, 95 % female) across 10 countries. Thematic analysis revealed several key themes: the burden of the physical symptoms (such as sicca), social isolation, negative impact on function, unpredictability of the disease, diverse coping strategies, and the challenges of navigating the healthcare system. Few studies addressed any bias in the recruitment of patients or analyses of data. SjD patients encounter a large variety of individual experiences in their illness that have important repercussions on quality of life. Understanding these experiences will help create a harmonized set of patient-centered outcomes to inform the generation of Outcome Measurement in Rheumatology (OMERACT) target domains in SjD.
B-cell activating factor (BAFF) of the Tumors Necrosis Factor (TNF) family is involved in the pathogenesis of Sjögren's disease (SjD). A functional variant (BAFF variant [BAFF-var]) of the BAFF gene (TNFSF13B), leading to increased levels of BAFF, has been described. The aim of this study was to investigate the association between BAFF-var and clinical phenotype and risk of SjD. A case-control study including cases from Paris Saclay and the Assessment of Systemic Signs and Evolution in Sjögren's syndrome (ASSESS) cohort and controls (blood donors from Etablissement Français du Sang [EFS]) was conducted. Genetic association analyses included only patients with European ancestry assessed by a principal component analysis using 24 ancestry-informative markers. We included 770 cases (420 from Paris Saclay and 350 from ASSESS) and 786 controls from EFS. Among them, 666 cases and 721 controls were found of European ancestry. We found that BAFF-var was significantly associated with higher soluble BAFF (sBAFF) level (1392.7 vs 1107.0 pg/mL, P < .001), and with increased occurrence of lymphoma (13% in patients with SjD with BAFF-var vs 5.8% in patients with SjD with BAFF-WT (wild-type), P = .013). BAFF-var remained independently associated with lymphoma after adjustment for rheumatoid factor, sex, and cumulative European League Against Rheumatism Sjögren's Syndrome Disease Activity Index (odds ratio [OR] 2.60, 95% CI: 1.14-5.47). By comparison with ancestry-matched controls, BAFF-var was also associated with SjD itself with a minor allele frequency of 0.061 in cases and 0.035 in controls (OR = 1.77, P = .0017). We found an association between BAFF-var and sBAFF levels, occurrence of lymphoma as well as occurrence of SjD itself. This variant could be a new biomarker for lymphoma risk in SjD.
Sjögren disease (SjD) is a systemic autoimmune condition that frequently involves the salivary glands. Salivary gland ultrasound (SGUS) has emerged as a promising noninvasive tool, and the Outcome Measures in Rheumatology (OMERACT) group has proposed a standardized semiquantitative scoring system. The aim of this study was to evaluate the diagnostic accuracy of OMERACT SGUS in routine clinical practice, using the 2016 American College of Rheumatology/European Alliance of Associations for Rheumatology (ACR/EULAR) criteria as the gold standard for diagnosis, and to compare its performance with salivary flow and Schirmer test. A prospective study was conducted including 103 consecutive outpatients referred for dryness evaluation. Two blinded sonographers performed SGUS of parotid glands (PGs) and submandibular glands (SMGs), applying the OMERACT 0-3 scale. Positivity was defined as a score ≥ 2 in at least 1 gland. Among 103 participants, 51 fulfilled the 2016 ACR/EULAR criteria. Overall, SGUS achieved sensitivity of 66.7% and specificity of 76.9%. PG analysis showed high specificity (92.3%) but lower sensitivity (49%), whereas SMGs demonstrated higher sensitivity (58.8%) but lower specificity (78.8%). Schirmer test and unstimulated whole salivary flow rate (UWSFR) showed sensitivities of 49% and 52.9%, respectively. Stimulated whole salivary flow rate had very high specificity (94.2%) but poor sensitivity (17.6%). In patients aged < 40 years, UWSFR sensitivity dropped markedly to 20% (vs age ≥ 40 years: 57.1%), whereas SGUS maintained stable performance. In real-world settings, SGUS using the OMERACT score demonstrates high specificity, particularly in PGs, and moderate sensitivity, outperforming UWSFR in younger patients. These findings support SGUS as a practical adjunct to established diagnostic tests and reinforce its potential role in refining the diagnostic workup of suspected SjD.
We aimed to assess the impact of socioeconomic status (SES) on risk of Sjögren's disease (SjD) compared with non-Sjögren's Sicca and population controls, and on the clinical features of SjD. A single-centre UK cohort provided participants with SjD (European Alliance of Associations for Rheumatology/American College of Rheumatology (EULAR/ACR) 2016, n=256) and non-Sjögren's Sicca (anti-Sjögren's syndrome type A (SSA)/Ro negative, n=175). Health Survey for England 2019 provided local population controls (n=972). English Indices of Multiple Deprivation (IMD) 2019 quintiles at recruitment and highest educational attainment defined SES.Adjusted logistic regression models evaluated associations between SES and diagnosis. Linear models assessed the impact of IMD on disease variables. Population controls were matched with age, sex and ethnicity to compare SES distributions. Across IMD and educational attainment, participants with SjD had lower SES status compared to Sicca (p=0.008 and p=0.018). Odds of SjD (vs Sicca) were highest in most deprived IMD quintile 1 and reduced by 74% in quintile 2 (OR 0.26 (0.12, 0.58), p<0.001).Immunoglobulin G and A levels were inversely associated with IMD. In SjD, each unit increase in IMD reduced IgG by 6.03% (-9.84%, -2.05%; p=0.003) and IgA by 6.46% (-10.87%, -1.60%; p=0.010).When compared with population controls, IMD was not a risk factor for SjD (p=0.257) whereas Sicca was associated with lower deprivation (p=0.003). Those with a degree level qualification had the highest odds of diagnosis (SjD or Sicca). Low SES is associated with increased risk of SjD compared to Sicca and with higher immunoglobulin levels. The Sicca cohort may be less deprived than the general population. The role of environmental factors in modulating salivary gland pathology requires further exploration.
Several studies reported an association between Sjögren's disease (SjD) and inclusion body myositis (IBM). However, the potential specificities of IBM when associated with SjD have been poorly investigated. Here, we compared the muscular inflammatory infiltrates between IBM patients with or without associated SjD. Formalin-fixed and paraffin-embedded muscle biopsies of patients with IBM, associated with SjD (IBM-SjD) and sporadic (sIBM) forms, from six French expert centres, were collected. Imaging mass cytometry (IMC) multiplex immunostaining (34 markers) was used to quantify and analyse inflammatory infiltrate composition. Supervised and unsupervised descriptive and comparative analyses were performed. Fourteen IBM-SjD and seven sIBM muscle samples were analysed. No statistically significant difference was encountered but some trends were pointed. IBM-SjD samples had a broader inflammatory infiltrate surface (median 4.8%, IQR: 1.4-8.6) than sIBM samples (median 1.6% IQR: 1.2-2.4). In both groups, the main inflammatory cells in muscle infiltrate were primarily macrophages and T cells. However, the proportion of plasma cells (14.7% IQR: 5.4-24.6 vs 8.5% IQR: 4.6-9.8) and B cells (3.1% IQR: 0.4-5.6 vs 0.5% IQR: 0.0-3.2) were higher in IBM-SjD patients. Using IMC on muscle biopsies, IBM-SjD and sIBM patients share common histological features, but there are notable distinctions (more extensive infiltrate, high numbers of B cells and plasma cells in IBM-SjD). These observations were exploratory and based on a small number of patients but may suggest IBM-SjD has distinct SjD-related pathophysiology compared with sIBM, and open to further research with potential diagnostic and therapeutic implications.
Sjögren's disease (SjD) is a chronic systemic autoimmune disease with heterogeneous glandular and extraglandular manifestations. Although aetiology and pathogenesis of SjD remains elusive, emergence of autoreactive T and B lymphocytes is crucial in disease development. In this study, the metabolome of patients with SjD was characterised to improve disease understanding and to identify biomarkers as tools to aid drug development. The metabolome was investigated in saliva, tears and plasma samples from two independent cohorts from Poland (PL) and the UK using a mass spectrometry screening platform with 4500 reference metabolites. The PL cohort included 30 healthy subjects and 32 patients with SjD. The UK cohort encompassed longitudinal samples from 13 healthy subjects and 12 patients with SjD. Patient heterogeneity was reflected in the metabolome across all three matrices (plasma, saliva and tears) with consistent disturbances in the amino acid metabolism and transport pathway. A biomarker signature was developed using both cohorts, which allowed to characterise patients with milder and more severe disease activity. The relevance of the biomarker signature was supported by the presence of metabolites linked to pathways such as gamma-glutamyl cycle, pyrimidine metabolism and sex steroid hormones, which have previously been described to be deregulated in patients with SjD and other autoimmune diseases. A plasma metabolome biomarker signature was developed that can be implemented in clinical studies by simple blood collection. The biomarker signature allows to characterise disease activity of patients with SjD at baseline and provides a basis for future studies to investigate its potential utility in monitoring therapeutic intervention.
To understand the ordering patterns of antinuclear antibody (ANA) multiplex testing in a single, large US Department of Defense (DoD) tertiary healthcare system. Records of patients with an ANA multiplex assay ordered over a 1-year period were evaluated in a large DoD hospital system. Duplicate tests and patients with a previously established autoimmune rheumatic disease (ARD) prior to the year of study were excluded. The remaining 2499 patients' charts were reviewed for clinical presentation, ordering specialty, ordering rationale, and whether subsequent rheumatology evaluations resulted in a new ARD diagnosis. The ANA multiplex assay was ordered most often by primary care and medicine subspecialties for > 100 reasons. In the ANA multiplex assay-negative group, 37/2228 (1.66%) individuals were diagnosed with a new ARD. In the ANA multiplex assay-positive group 37/271 (13.7%) individuals were diagnosed with a new ARD. Sjögren disease, systemic lupus erythematosus, and undifferentiated connective tissue disease were the most common newly diagnosed ARDs in the ANA multiplex assay-positive group. Rheumatoid arthritis and seronegative spondyloarthritis were the most common new ARD diagnoses in the ANA multiplex assay-negative group. In this study, 97% of the ordered ANA assays did not lead to an ARD diagnosis. This study demonstrates frequent utilization of the ANA multiplex assay in the evaluation of nonspecific signs and symptoms, with a low rate of ANA-associated ARDs suggesting a need for implementation of strategies to improve understanding of appropriate clinical contexts that warrant ANA testing.
The reported incidence and mortality of connective tissue diseases (CTDs) in England has been inconsistent in the literature. Our objective was to describe current trends in the incidence and mortality of systemic lupus erythematous (SLE), Sjögren's disease (SjD), systemic sclerosis (SSc), idiopathic inflammatory myopathies (IIM) and mixed connective tissue disease (MCTD). We conducted a retrospective population-level study using primary care records in England via the Clinical Practice Research Datalink. We included individuals ≥18 years old with new CTD diagnoses between 2012 and 2023. Our outcomes were incidence and all-cause mortality, which included age-standardized mortality rates (ASMRs), standardized mortality ratios and hazards over time using flexible parametric models. There was a total of 22 829 incident CTD diagnoses (81.1% female, median age 57). The age and sex-standardized incidence of SLE and SSc fell over the study period 2012-2023 (SLE: 4.32-3.29 per 100 000 person years [py] and SSc: 2.33-1.86 per 100 000 py), whereas SjD and MCTD incidence remained relatively stable. In contrast, IIM diagnoses rose from 3.23 to 4.31 per 100 000 py. ASMRs across the study period were highest for IIM (27.83 per 1000 py), followed by SSc (24.43), SLE (16.74), MCTD (16.27) and lowest for SjD (9.70). Our findings indicated a fall in the incidence of SLE, a simultaneous rise in IIM incidence, and high all-cause mortality within IIM and SSc cohorts. Our study acknowledges the changing landscape of CTDs in England and will aid healthcare resource planning for this vulnerable population.
Anti-Ro/SS-A antibodies are prevalent across systemic autoimmune rheumatic diseases (SARDs) and may signify a distinctive phenotype. This study aimed to identify protein biomarkers associated with symptom burden and health-related quality of life (HR-QoL), and use protein-based stratification to identify clinically meaningful clusters and inflammatory pathways implicated. Anti-Ro positive SARD patients were enrolled in a 6-month pilot study. HR-QoL was determined using a patient-reported visual analogue scale, and symptom burden was assessed with the EULAR Sjögren's Syndrome Patient Reported Index (ESSPRI). Proximity extension immunoassays measured normalized protein expression (NPX) across 92 inflammatory proteins. Linear regression identified proteins linked to patient outcomes. Unsupervised hierarchical clustering of baseline NPX identified patient clusters. Functional protein association networks were visualized using String V.12.0. Diagnostic groups showed no differences in HR-QoL or physician global assessment (PhGA). Poor HR-QoL and high symptom burden correlated with downregulated inflammatory proteins, while PhGA correlated with upregulated proteins. Two distinct clusters were identified; Cluster 1, 'low expression cluster' exhibited higher symptom burden and more impaired HR-QoL, while Cluster 2, 'high expression cluster' correlated with a higher physician global assessment (PhGA). Key hub proteins included TGF-β1, CXCL-8, and CCL-2. This study identified patient clusters across the Ro-positive SARD, linking symptom burden to specific proteomic profiles. Unraveling novel protein networks associated with symptom burden and poor HR-QoL may identify therapeutic targets, which address patient-reported outcome measures (PROMs) across several disease indications.
To explore sex differences in patient-reported outcome measures (PROMs) and clinical parameters in patients with Sjögren's disease (SjD). Consecutive patients with clinical diagnosis of SjD, enrolled in the prospective RESULT cohort or retrospective DiagnoSS registry, who fulfilled 2016 ACR/EULAR classification criteria, were included. PROMs evaluating sicca symptoms, fatigue, pain and health-related quality of life (HR-QoL), and clinical parameters including salivary and ocular gland function, salivary gland ultrasound (SGUS) and biopsy outcomes, physical examination results, serological parameters, systemic disease activity and damage were compared between female and male patients. Of the 405 SjD patients, 360 (89%) were female and 45 (11%) were male. Females had earlier onset of symptoms (median 37 vs. 51 years), longer diagnostic delay (5 vs. 3 years), scored worse on PROMs assessing sicca symptoms (e.g. ESSPRI dryness median 7 vs. 5), had lower salivary gland function (SWS, UWS; UWS<0.1ml/min: 69% vs. 44%), and more tender points than male patients. ESSDAI total score did not differ, but female patients less often had pulmonary (1.7% vs. 6.7%) and peripheral nervous system activity (3.4% vs. 11.1%) than male patients. Clinical parameters including ocular tests, SGUS (Hocevar), biopsy parameters, immunological serology and damage (SSDDI) did not differ. HR-QoL (SF-36, EQ-5D-5L: index median 0.76 vs. 0.74) and PASS (72% vs. 70%) were comparable between sexes. In this cohort of SjD patients from daily clinical practice, female and male patients showed distinct patterns of experienced symptoms and disease manifestations. The overall impact of SjD on HR-QoL was similar.
This study aimed to investigate the relationship between specific autoantibodies, particularly anti-Ro52, and the development of interstitial lung disease (ILD) in patients with autoimmune diseases (AID), with the goal of identifying potential biomarkers for the early detection and management of ILD. A retrospective cohort study was conducted at Peking Union Medical College Hospital, involving 2,021 AID patients who underwent antinuclear antibody (ANA) testing between 2017 and 2019. Clinical and serological data were collected to assess the presence of ILD and its association with specific autoantibodies. Least absolute shrinkage and selection operator (LASSO) regression was used to identify predictors of ILD. Among the 2,021 patients, ILD prevalence varied across AID subgroups, with the highest rates observed in idiopathic inflammatory myopathies (IIM), overlap syndrome, and systemic sclerosis. Anti-Ro52 was significantly more frequent in IIM patients with ILD compared to those without ILD (83.0% vs. 37.8%, p<0.0001). Anti-RNP was detected at a significantly higher rate in lupus-ILD patients. Additionally, positivity rates of anti-SSA/Ro60 and anti-CENP B were inversely associated with ILD in Sjögren's disease and systemic sclerosis, respectively. LASSO regression analysis identified anti-Ro52, age, and anti-MDA5 as significant predictors of ILD development in IIM. Anti-Ro52 positivity was associated with a more than two-fold increased risk of ILD progression in mixed connective tissue disease. Anti-Ro52, together with age and anti-MDA5, was identified as a significant predictor of ILD in IIM patients. This study highlights the potential of autoantibodies as biomarkers for early detection and management of ILD in AID patients.
Fetal autoimmune congenital heart block is a rare but life-threatening condition that is difficult to predict. This study sought to identify a serological biomarker predictive of autoimmune congenital heart block in pregnancies at risk due to maternal systemic lupus erythematosus, Sjögren's disease, undifferentiated connective tissue disease, or a history of congenital heart block offspring. This case-control study analysed maternal blood samples from pregnancies affected and unaffected by autoimmune congenital heart block from two centres (The Hospital for Sick Children, Canada, and The University of Padua, Italy). Serum samples collected across varying gestational ages were used for biomarker discovery, verification, and validation. The key inclusion criterion was a positive clinical test for maternal anti-Sjögren's syndrome-related antigen A/Ro autoantibodies, and the key exclusion criterion was structural congenital heart disease associated with heart block. Cases were pregnancies that resulted in fetal or neonatal congenital heart block and controls were pregnancies that resulted in offspring with a normal heart rhythm. Two-dimensional western blotting was used to identify maternal autoantibodies targeting fetal cardiac proteins, using fetal heart tissue and stem-cell-derived cardiomyocytes. Findings were validated using commercial proteins. Sensitivity and specificity for predicting fetal heart block outcomes were assessed using receiver-operating characteristic curves. The primary study outcomes were the presence and specificity of anti-cardiac autoantibodies in autoimmune congenital heart block cases versus controls, the association between specific autoantibodies and congenital heart block development, and the predictive accuracy of identified autoantibodies. This study did not involve individuals with lived experience in the study design or implementation. Serum samples were collected between Jan 1, 2010, and Dec 31, 2020, in the discovery cohort (The Hospital for Sick Children), between Aug 1, 1999, and Dec 31, 2019 in the
Rheumatic diseases may impair reproductive success and pregnancy outcomes, but systematic evaluations across diseases are lacking. We conducted a nationwide cohort study to examine the impact of rheumatic diseases on reproductive health measures, comparing the impacts with those of other immune-mediated diseases (IMDs). Out of all of the 5 339 804 Finnish citizens, individuals born 1964-1984 and diagnosed with any of the 19 IMDs before age 30 (women) or 35 (men) were matched with 20 controls by birth year, sex, and education. We used data from nationwide health registers to study the impact of IMDs on reproductive health measures, such as reproductive success and, for women, ever having experienced adverse maternal and perinatal outcomes. Several of the rheumatic diseases, particularly SLE, JIA, and seropositive RA, were associated with higher rates of childlessness and fewer children. The risks for pre-eclampsia, newborns being small for gestational age, preterm delivery, non-elective Caesarean sections, and need of neonatal intensive care were increased in many IMDs. Particularly, SLE, SS, type 1 diabetes, and Addison's disease showed >2-fold risks for some of these outcomes. In most rheumatic diseases, moderate (1.1-1.5-fold) risk increases were observed for diverse adverse pregnancy outcomes, with similar effects in IBD, celiac disease, asthma, ITP, and psoriasis. Rheumatic diseases have a broad impact on reproductive health, with effects comparable with that of several other IMDs. Of the rheumatic diseases, SLE and SS conferred the largest risk increases on perinatal adverse event outcomes.
Sjögren's is a chronic systemic autoimmune disease characterised by dryness symptoms (eyes, mouth, skin), alongside other systemic manifestations such as fatigue, muscle and joint pain, neuropathies and organ involvement. Despite its prevalence, research into the patient perspective of Sjögren's is limited. This study aimed to better understand the burden, unmet needs and treatment satisfaction among adults with Sjögren's. Data were collected using a cross-sectional survey of adult patients with Sjögren's across China, France, Germany, Italy, Japan, Spain, the UK and the USA (December 2023 to September 2024). Patients were recruited via physicians or patient advocacy organisations. The Work Productivity and Activity Impairment (WPAI) tool assessed work-related productivity and daily activity impact. Analyses were descriptive. 1155 patients completed the survey. Mean (SD) age was 54.5 (13.0) years; 88.2% were female and 95.3% white. Most frequently reported symptoms were dry mouth, dry eyes, dry skin, physical fatigue/tiredness and joint stiffness/soreness. High emotional burden from Sjögren's (rating 5-7 out of 7) was reported by 57.7%. WPAI scores showed 46.6% work and 48.4% activity impairment. Of those receiving prescription therapy, 77.2% were dissatisfied and/or believed disease control could improve. Among those not fully satisfied, 52.9% felt current treatments only addressed symptoms, not the underlying systemic nature of Sjögren's. The Spotlight on Sjögren's study reveals the substantial, multifaceted burden of Sjögren's, extending beyond dryness to significantly impair physical, emotional and functional well-being. Findings underscore the need for comprehensive, patient-centred care and therapies addressing both symptoms and the underlying systemic disease.
Immunocompromised Sjögren's disease-(SjD) patients are susceptible to herpes zoster reactivated infection-(HZ/shingles), yet data on the recombinant zoster vaccine-(Shingrix®/RZV) in these patients are limited. To assess RZV humoral/cellular immunogenicity and safety in immunocompromised SjD patients. Randomized double-blind placebo-controlled study comprising 67 immunocompromised SjD patients and 201 age-/sex-balanced non-immunosuppressed controls. SjD patients were randomized to receive vaccine-(SjD-V) or placebo-(SjD-P) on day-0-(D0) and D42. SjD-P were immunized after unblinding on D84 and D126. Controls were vaccinated on D0 and D42. Adverse events-(AEs) and disease activity were monitored. Humoral immunogenicity was assessed by anti-gE concentrations, with seroconversion defined as ≥4-fold increase from baseline to 6-weeks after the 2nd RZV dose. gE-specific CD4+ T cells were counted in ≅10% of participants. Vaccine impact on SjD symptoms/biological parameters was explored. SjD and controls were comparable regarding age [55.0 (48.3-63.8) vs. 55.0 (52.0-64.0) years; P = 0.087] and sex (P = 0.303). Seroconversion rate was lower in SjD than controls (90.6% vs. 99.5%; P < 0.001), with reduced geometric-mean-titer-(GMT) [7.1 (5.3-9.6) vs. 12.6 (11.4-13.9) mIU/mL; P < 0.001] and factor-increase-GMT [23.9 (16.0-35.8) vs. 70.4 (58.8-84.4); P < 0.001] in SjD. The cellular response was comparable between SjD patients and controls (P > 0.05). Disease activity, SjD symptoms/biological parameters remained stable (P > 0.05). No serious vaccine-related AEs occurred. RZV showed a favorable safety profile in immunocompromised SjD patients. Despite the high seroconversion rate, the response was significantly lower in magnitude compared to controls. This may compromise long-term immunity, underscoring the need for optimizing immune responses in this population (ClinicalTrials.gov-NCT05879419).
Thrombocytopaenia, anasarca, fever, reticulin fibrosis, renal dysfunction and organomegaly (TAFRO) syndrome has been reported to be associated with anti-SS-A antibodies, which activate type I interferon (IFN) signalling. We propose a subclassification of TAFRO syndrome based on the anti-SS-A antibody status, with the aim of identifying effective treatment strategies. We reviewed TAFRO syndrome cases from the PubMed/MEDLINE databases from January 1977 to October 2024. The information on concomitant autoimmune diseases, the presence of anti-SS-A antibodies, serum IgG levels, treatment courses and clinical outcomes was collected and retrospectively analysed. Patients were stratified according to anti-SS-A antibody status, and response to tocilizumab (TCZ) or rituximab (RTX) was evaluated. Among 212 cases, 27 had concomitant autoimmune diseases, with Sjögren's disease (SjD) being the most common. Anti-SS-A antibody positivity was observed in 37 cases, of which 12 fulfilled the classification criteria for SjD. RTX was significantly more effective in anti-SS-A antibody-positive patients than in antibody-negative patients (88.9% vs 16.7%, p=0.011), whereas therapeutic response to TCZ was not affected by anti-SS-A antibody status. Serum IgG levels were significantly higher in anti-SS-A antibody-positive patients than in antibody-negative patients (p=0.020). TAFRO syndrome shows clinical heterogeneity and anti-SS-A antibody status may represent one potential factor associated with treatment response. Further studies are needed to confirm these findings and clarify the underlying mechanisms.
To investigate pregnancy outcomes in women with autoimmune rheumatic diseases (ARD) in the Italian prospective cohort study P-RHEUM.it. Pregnant women with different ARD were enrolled for up to 20 gestational weeks in 29 Rheumatology Centres for 5 years (2018-2023). Maternal and infant information were collected in a web-based database. We analysed 866 pregnancies in 851 patients (systemic lupus erythematosus was the most represented disease, 19.6%). Maternal disease flares were observed in 135 (15.6%) pregnancies. 53 (6.1%) pregnancies were induced by assisted reproduction techniques, 61 (7%) ended in miscarriage and 11 (1.3%) underwent elective termination. Obstetrical complications occurred in 261 (30.1%) pregnancies, including 2.3% pre-eclampsia. Two cases of congenital heart block were observed out of 157 pregnancies (1.3%) with anti-Ro/SSA. Regarding treatments, 244 (28.2%) pregnancies were treated with glucocorticoids, 388 (44.8%) with hydroxychloroquine, 85 (9.8%) with conventional synthetic disease-modifying anti-rheumatic drugs and 122 (14.1%) with biological disease-modifying anti-rheumatic drugs. Live births were 794 (91.7%), mostly at term (84.9%); four perinatal deaths (0.5%) occurred. Among 790 newborns, 31 (3.9%) were small-for-gestational-age and 169 (21.4%) had perinatal complications. Exclusive maternal breast feeding was received by 404 (46.7%) neonates. The Edinburgh Postnatal Depression Scale was compiled by 414 women (52.4%); 89 (21.5%) scored positive for emotional distress. Multiple factors including preconception counselling and treat-to-target with pregnancy-compatible medications may have contributed to mitigate disease-related risk factors, yielding limited disease flares, good pregnancy outcomes and frequency of complications which were similar to the Italian general obstetric population. Disease-specific issues need to be further addressed to plan preventative measures.