Objective This study aimed to assess the prevalence of comorbidities among patients with rheumatoid arthritis (RA) and identify factors associated with it. Methods A cross-sectional study was conducted at 2 tertiary care hospitals among 653 patients with RA. Data on demographics, poor prognostic factors (high erythrocyte sedimentation rate [ESR], C-reactive protein [CRP], rheumatoid factor, anticyclic citrullinated peptide antibody titers, and Disease Activity Score in 28 joints [DAS28] > 5.1), and comorbidities were collected through a structured questionnaire and medical record review. Comorbidities were quantified by the Charlson Comorbidity Index (CCI). Logistic regression analyses were used to identify associated factors. Results A total of 646 (98.9%) patients had ≥ 1 comorbidity. The most prevalent were dyslipidemia (75.8%), obesity (58.7%), hypertension (42.7%), type 2 diabetes mellitus (30.3%), and osteoporosis (OP; 15.6%). Age ≥ 45 years was independently associated with coronary artery disease (odds ratio [OR] 9.71, 95% CI 1.91-178.00), OP (OR 19.60, 95% CI 5.96-121.00) and infectious diseases (OR 1.60, 95% CI 1.03-2.54). Female sex was associated with lower cardiovascular risk (OR 0.27, 95% CI 0.11-0.62), whereas female sex was associated with increased odds of OP (OR 3.55, 95% CI 1.71-8.37) and gastrointestinal (GI) disorders (OR 2.18, 95% CI 1.37-3.56). The use of targeted synthetic and biologic disease-modifying antirheumatic drugs increased the risk of infection (OR 14.80 and 4.11, respectively). High DAS28-CRP and ESR values were linked to GI comorbidities. The CCI survival index was significantly lower in older patients (≥ 45 years; mean 68.7 [SD 26.7]) than in younger patients (mean 93.3 [SD 6.7], P < 0.001). Conclusion The prevalence of multimorbidity is high among patients with RA in Bangladesh, particularly early cardiovascular disease risk.
Rheumatoid arthritis (RA) and major depressive disorder (MDD) exhibit significant comorbidity, with shared pathological mechanisms such as inflammation and abnormal lipid metabolism. However, the specific molecular features and functional pathways linking the two diseases remain unclear. This study integrated public transcriptomic data from five MDD and five RA cohorts. Lipid metabolism-related module genes were screened in MDD cohorts and intersected with RA-upregulated differentially expressed genes to construct a candidate set. LASSO regression and machine learning (XGBoost, Random Forest) were used for feature selection and model construction. Functional exploration included protein-protein interaction network analysis, immune infiltration analysis, and multi-cohort validation. To experimentally test the proposed lipid-immune link and a potential neuron-to-synovium axis, we established an in vitro model. Hippocampal HT-22 neurons were subjected to combined glucocorticoid and saturated fatty acid stimulation to mimic MDD-associated stress-lipotoxicity. The conditioned medium (CM) from these neurons was then applied to human fibroblast-like synoviocytes (FLS). The inflammatory and functional responses of FLS were assessed through qPCR, ELISA, and Western blot. A nine-gene lipid-immune signature (ANXA3, IL18, CD59, TNFSF13B, BMX, WASF1, SLC8A1, COMMD8, NXT2) was identified. It showed excellent discriminative performance in independent RA cohorts (AUC 0.86-1.00) but weaker performance in MDD cohorts (AUC 0.55-0.65). TNFSF13B, IL18, and CD59 were consistently identified as core hubs. The signature's expression correlated significantly with immune cell infiltration in RA. Critically, our in vitro validation demonstrated that CM from lipid-stressed neurons directly activated FLS. This was evidenced by: (i) significant upregulation of CD59 mRNA and protein levels (via qPCR and Western blot); (ii) elevated secretion of key inflammatory mediators IL-6 and MMP3 (via ELISA); and (iii) enhanced migratory capacity of FLS. These data support a putative paracrine communication axis from stressed