Para médicos · reumatologia
Resumos de artigos, podcasts e newsletters sobre Síndrome Antifosfolípide, para atualização médica.
A newsletter aborda inovações do EULAR 2026, destacando a embolização da artéria genicular como uma alternativa promissora e segura para o manejo da dor na osteoartrite de joelho refratária. O conteúdo também analisa a persistência da sarcopenia em pacientes com artrite reumatoide controlada e os desafios da inércia terapêutica no tratamento da hipertensão arterial pulmonar em pacientes com esclerose sistêmica.
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 destaca que a infecção por SARS-CoV-2 aumenta a positividade de anticorpos antifosfolípides em gestantes com SAF, especialmente no terceiro trimestre, embora o manejo padrão pareça mitigar desfechos adversos graves. Paralelamente, apresenta dados robustos de fase 3 que posicionam o obinutuzumabe como uma terapia eficaz para o LES sistêmico, alcançando altas taxas de resposta clínica e redução sustentada do uso de corticoides. O informativo também revisa casos de hipermobilidade articular e novas diretrizes internacionais para o manejo de doenças reumáticas.
Obstetric APS remains a major cause of maternal-fetal morbidity. Advances in understanding placental inflammation have expanded potential therapeutic targets, but standardized treatment remains limited. Optimal care requires risk-stratified, multidisciplinary management and further research to improve pregnancy outcomes.
A newsletter destaca que adolescentes com vasculite por IgA apresentam maior risco de púrpura persistente e proteinúria, exigindo vigilância renal redobrada. Na espondiloartrite axial, o uso de upadacitinibe mostrou-se superior à troca por outro anti-TNF ou anti-IL-17 após falha terapêutica inicial. O conteúdo também aborda o diagnóstico de eritema ab igne e a identificação de dano miocárdico subclínico no lúpus através de técnicas avançadas de imagem.
Background Primary Antiphospholipid Syndrome (PAPS) is a systemic autoimmune disorder characterized by arterial and/or venous thrombosis and obstetric morbidity. Arterial thrombosis, although less frequent than venous events, is associated with substantial morbidity and mortality. Alongside environmental and acquired factors, several genetic polymorphisms affecting coagulation, endothelial function, fibrinolysis, and platelet activation have been investigated in relation to thrombotic risk. Clarifying their contribution may help refine hypotheses for risk stratification. Objectives To systematically review the available evidence on genetic polymorphisms associated with arterial thrombosis in PAPS and to evaluate their reported associations with arterial thrombotic manifestations. Search methods Electronic searches were conducted in MEDLINE, the Cochrane Library, ClinicalTrials.gov, the GWAS Catalog, the Genetic Association Database, and Google Scholar for studies published up to November 2024. Selection criteria Case–control, cohort, and genome-wide association studies were included if they assessed genetic variants in confirmed PAPS with arterial thrombosis. Comparators included healthy controls, patients with other autoimmune diseases, or APS without arterial events. Data collection and analysis Two reviewers independently screened studies, extracted data, and assessed risk of bias using the Cochrane and ROBINS-I tools. Due to substantial heterogeneity in study design, populations, and outcome definitions, meta-analysis was not feasible, and results were summarized narratively. Main results Eighteen studies published between 1994 and 2023 were identified, of which seventeen contributed to the genetic association synthesis. Variants in platelet membrane glycoproteins (GPIa 807T, GPIbα Kozak TC, and combined GPIa 807T plus GPIIb/IIIa PlA2) were the most frequently reported positive associations with arterial thrombosis. PAI-1 (4G) and MTHFR (C677T) showed inconsistent and weak associations, while the EPCR (PROCR) H1 haplotype was negatively associated with arterial thrombosis in isolated analyses. Classical thrombophilic mutations, including Factor V Leiden and
Objective International criteria for antiphospholipid syndrome (APS) include lupus anticoagulant (LA), anticardiolipin (aCL) IgG and IgM, and anti–β2‐glycoprotein I (β2GPI) IgG and IgM. However, evidence supporting their prognostic value or treatment efficacy in improving live birth rates is limited. The Lancet series on miscarriage recommends testing only for LA and aCL, excluding β2GPI. We aimed to examine whether commercially available antiphospholipid antibody (aPL)‐related tests have a prognostic value for obstetric APS. Methods This prospective cohort study enrolled 1,237 pregnant women between July 2021 and March 2024. Women using heparin, including those with an obstetric APS diagnosis before pregnancy, were excluded. Pregnancy outcomes were followed until December 2024. The aPL‐related tests comprised LA (diluted activated partial prothrombin time and diluted Russell's viper venom time [LA‐RVVT]), aCL IgG, IgM, anti‐β2GPI IgG, IgM, anti β2GPI domain I IgG, phosphatidylserine‐dependent antiprothrombin IgG, IgM, protein S, and coagulation factor XII activity. Results The prevalence rates of early‐onset preeclampsia, intrauterine fetal death (IUFD), and small for gestational age were 1.4% (17), 0.7% (9), and 0.9% (11), respectively. Logistic regression analysis revealed that LA‐RVVT and anti‐β2GPI IgG were each predictor of early‐onset preeclampsia and IUFD. The area under the curve for these conditions increased to about 0.8 when combined with a history of preeclampsia or IUFD, respectively. Conclusion LA‐RVVT, anti‐β2GPI IgG, complications including hypertension, and a history of IUFD were valuable in identifying obstetric APS. The variation in test results across facilities limits the ability to establish consistent prognostic or treatment value for each aPL.
Objective Antiphospholipid syndrome (APS) is a thromboinflammatory disorder characterized by clinical and mechanistic heterogeneity that complicates early diagnosis and hinders targeted treatment. We aimed to identify distinct molecular endotypes among antiphospholipid antibody (aPL)–positive patients using whole‐blood transcriptomics. Methods Whole‐blood RNA sequencing was performed on 174 aPL‐positive patients, including those with primary APS (n = 102), secondary APS (n = 29), and aPL positivity without classifiable APS (n = 43). Unsupervised machine learning and immune cell deconvolution defined transcriptomic clusters and immune landscapes. Results Four transcriptionally distinct clusters were identified. At one end of the spectrum, cluster 1 showed up‐regulation of ribosomal and metabolic pathways and down‐regulation of mechanistic target of rapamycin (mTOR), NETosis, and Hippo/interleukin‐6 (IL‐6) signaling. In contrast, cluster 4 exhibited the opposite pattern, with strong up‐regulation of mTOR, NETosis, and Hippo/IL‐6 signaling. Cluster 2 demonstrated modest enrichment in messenger RNA processing and amino acid metabolism, and cluster 3 showed biosynthetic suppression with mild Hippo/IL‐6 activation. Clinically, cluster 4 stood out with higher IgG anticardiolipin and anti–β 2 ‐glycoprotein I positivity, elevated neutrophil counts, and increased urine protein‐to‐creatinine ratios. Immune deconvolution revealed distinct cell type profiles: cluster 1 was lymphoid predominant; cluster 2 had a balanced composition; cluster 3 was enriched in Treg cells, natural killer cells, macrophages, mast cells, and memory B cells; and cluster 4 was dominated by myeloid cells, including neutrophils, eosinophils, and dendritic cells. Distinct immune pathway activations were linked to clinical features, including white matter lesions, seizures, and cardiac valve disease. Conclusion This study reveals four endotypes of aPL‐positive patients, a step toward personalized medicine for APS through pathway‐informed stratification and therapy.
Objective ATP is released from platelets through both degranulation and pannexin‐1 (PANX1) channels. ATP then activates P2X receptors to amplify platelet activation via calcium‐dependent signaling. The objective of this study was to evaluate the role of platelet PANX1 channels in the pathophysiology of antiphospholipid syndrome (APS), an acquired thromboinflammatory disorder characterized by platelet‐activating antiphospholipid antibodies. Methods Extracellular ATP release was measured in platelets isolated from patients with persistently positive antiphospholipid antibodies (n = 36), patients with systemic lupus erythematosus (n = 10), and healthy controls (n = 16). In some assays, purified platelets were pretreated with the PANX inhibitor carbenoxolone. Platelet signaling, P‐selectin exposure, and aggregation were assessed. Results Basal ATP release was significantly higher in APS platelets than in controls ( P < 0.0001) and normalized in the presence of carbenoxolone ( P = 0.03). Carbenoxolone also reduced platelet ATP release and surface P‐selectin expression induced by thrombin ( P = 0.002 and P = 0.02, respectively) and convulxin ( P = 0.0001 and P = 0.0012). Control platelets stimulated with IgG from patients with APS demonstrated enhanced phosphorylation of PANX1 at tyrosine‐308 ( P = 0.03), which was accompanied by enhanced ATP release ( P = 0.0004). APS IgG boosted ADP‐induced aggregation ( P = 0.0011), which was reduced by carbenoxolone ( P = 0.0007). The calcium chelator BAPTA‐AM decreased APS IgG–mediated ATP release ( P = 0.03), P‐selectin expression ( P = 0.0005), and aggregation ( P = 0.0007). Desensitizing P2X1 receptors with α,β‐MeATP decreased APS IgG–induced P‐selectin expression ( P = 0.0002) and aggregation ( P = 0.01). Conclusion PANX1 channels appear to be important mediators of platelet activation in APS. Agents that block PANX1 may
Systemic lupus erythematosus (SLE) is a multisystem autoimmune disease. Patients with lupus nephritis (LN) complicated by thrombotic microangiopathy (TMA) exhibit high mortality and poor renal outcomes. Eculizumab, a humanized monoclonal antibody inhibiting terminal complement C5 activation, has been recommended for the treatment of TMA caused by alternative complement pathway activation. This study evaluated the clinical efficacy of eculizumab in pediatric LN-associated TMA. We retrospectively analyzed children diagnosed with LN-TMA from July 2009 to January 2025. All patients met the 2019 EULAR/ACR SLE classification criteria and were aged < 18 years. TMA diagnosis required microangiopathic hemolytic anemia, thrombocytopenia, and organ involvement, excluding TTP (ADAMTS13 deficiency), Shiga toxin-associated HUS, antiphospholipid antibody syndrome, infections, hypertension, or drug-induced TMA. Overall survival, renal response, and hematologic recovery were analyzed. Among 22 LN children with TMA, 4 received ≥ 1 dose of eculizumab (eculizumab group), while 18 served as controls. Baseline characteristics showed no significant differences. Eculizumab treatment was initiated approximately 7 days following TMA diagnosis. By week 1, the eculizumab group demonstrated significant reductions in serum creatinine and improved eGFR, sustained through 16 weeks, whereas controls showed delayed improvement by week 8. Time to partial renal response was shorter with eculizumab (1.67 vs. 3.64 months, P < 0.05). Complete renal remission rates trended higher with eculizumab (100% vs. 50.0%, P = 0.29). Kaplan-Meier analysis confirmed superior 1-year complete remission rates in the eculizumab group (P = 0.003). Hemoglobin recovery was faster with eculizumab. No deaths or severe infections occurred, affirming its safety. In pediatric LN with TMA, eculizumab outperforms conventional therapy by accelerating renal recovery. Early use-after excluding TTP, infections, and drug-related causes-may mitigate renal damage and improve outcomes. Given that this is a retrospective study with a small sample size, the findings require
We recently identified four SLE clusters based on 13 autoantibodies used in clinical practice. In this prospective cohort study, we investigate the incidence of major cardiovascular events (MACE) and venous thromboembolism (VTE) in SLE patients stratified by clusters. Clusters were compared with each other and to matched controls. Clusters were defined at baseline: cluster 1 dominated by anti-SSA/SSB, cluster 2 by anti-nucleosome/Sm/RNP/dsDNA, cluster 3 by aPL and cluster 4 negative for all 13 autoantibodies. SLE clinical data were collected at enrolment. Vascular outcomes were prospectively retrieved from the National Patient Register using ICD codes. Each patient was matched on birth/sex/residence to 10 controls from the Total Population Register. Subjects with previous vascular events were excluded. Hazard ratios (HRs) and 95% CIs from Cox proportional hazards models estimated the age-adjusted relative risks of incident vascular events. We included 461 SLE patients, mean follow-up 12.2 ± 5.6 years. Compared with reference clusters, cluster 3 (n = 154) had the highest relative risk for MACE (HR 1.91 (95% CI: 1.01-3.58)) and VTE (HR 2.69 (95% CI: 1.05-6.9)). Cluster 2 (n = 105) had high risk for heart failure and VTE, similar to cluster 3, despite younger age. The lowest incidence of vascular events was observed in cluster 4 (n = 61) in comparison to the other clusters. We observed differences regarding the incidence of MACE and VTE during 12 years of follow-up for four autoantibody-defined clusters. The highest incidences were seen in the aPL-dominated cluster, while the lowest were detected in the autoantibody-negative cluster.
Although the existence of antiphospholipid antibodies (aPL) has been extensively documented as a risk factor for thrombocytopenia, hemolytic anemia, and recurrent miscarriage, their contribution to renal damage in the context of the systemic lupus erythematosus (SLE) is yet to be defined. This meta-analysis investigated the association between aPL and renal injury among patients with SLE. A systematic literature search was conducted to determine publications that examined the relationship between the level of aPL and renal functioning in SLE patients in four electronic databases (PubMed, Cochrane Library, Embase, and Web of Science). Funnel plots and Egger's test were utilized to assess the presence of publication bias. Sensitivity analysis and the trim-and-fill method were used in the evaluation of the stability of the results. Subgroup analyses were performed according to study design, geographic region, aPL subtype, publication date, and pathological type of lupus nephritis. Also, the cumulative meta-analyses were conducted by ranking the studies based on the year of publication, sample size, and the Newcastle-Ottawa Scale score. A total of 34,353 publications were retrieved up to September 12, 2025. After screening, a total of 70 studies (18 case-control, 23 cohort, and 29 cross-sectional) involving 12,456 SLE patients were included. The pooled OR for renal injury in aPL-positive versus aPL-negative patients was 2.09 (1.70-2.58). Subgroup analysis revealed anti-cardiolipin (aCL), lupus anticoagulant (LA), and antiphospholipid syndrome significantly increased the risk of renal injury compared with control groups, 108with OR of 1.71 (1.34-2.18), 2.43 (1.64-3.61), 2.07 (1.48-2.89), respectively. In contrast, no statistically significant increase in renal injury risk was observed in groups positive for anti-β2-glycoprotein I and aPS/PT. Cumulative meta-analyses consistently demonstrated an increased risk of renal injury in aPL-positive patients, and this association remained
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 detalha as atualizações do ACR 2025, evidenciando que a resistência insulínica é o fator causal da hiperuricemia na gota e reforçando a segurança de diversos imunobiológicos durante a gestação e lactação. Além disso, aborda a eficácia de imunossupressores em manifestações não-critério da síndrome antifosfolípide e novas perspectivas sobre o metabolismo do ferro nas espondiloartrites.
A newsletter aborda a importância de minimizar o uso de glicocorticoides na nefrite lúpica para evitar danos cumulativos, destacando novos critérios de acesso a biológicos no Brasil. Apresenta também o anti-HDGFL1 como um novo autoanticorpo promissor para o diagnóstico de miosites soronegativas e discute o papel protetor dos inibidores de SGLT-2 em vasculites associadas ao ANCA.