Background Rheumatoid arthritis (RA) is a chronic inflammatory disease associated with metabolic reprogramming of immune cells. Although inflammatory cytokines have been extensively studied, the effects of disease-modifying therapies including methotrexate, infliximab and their combination on serum immunometabolic biomarkers remain incompletely understood. Methods This cross-sectional study included newly diagnosed RA patients, patients receiving MTX monotherapy, patients receiving MTX plus infliximab, and healthy controls. Serum levels of tumor necrosis factor-alpha (TNF-α), interleukin-10 (IL-10), lactate, citrate, and succinate dehydrogenase (SDH) activity were measured. Disease activity was evaluated using the Disease Activity Score in 28 joints (DAS28). Statistical analyses, hierarchical clustering, correlation and network analyses, principal component analysis (PCA), and exploratory structural equation modeling (SEM) were used to investigate immunometabolic relationships and treatment-associated changes. Results Newly diagnosed RA patients showed significantly elevated TNF-α, IL-10, lactate, SDH activity, TNF-α/IL-10 ratio, and DAS28, alongside reduced citrate levels compared with controls and treated patients. Combined MTX and infliximab therapy demonstrated the greatest improvement in inflammatory and metabolic biomarkers and the lowest disease activity. Multivariate analyses identified TNF-α, lactate, and DAS28 as major contributors to disease-associated variation, while citrate displayed an opposing metabolic pattern. Correlation and network analyses identified TNF-α as a central link between inflammation, metabolic remodeling, and disease severity. SEM suggested that treatment-associated reductions in TNF-α were related to decreased glycolytic activity, improved mitochondrial metabolism, and reduced disease activity. Conclusion RA involves coordinated inflammatory and metabolic dysregulation. Combined MTX and infliximab therapy appears more effective than MTX alone in restoring immunometabolic balance.
C/EBPδ, encoded by CEBPD, regulates inflammatory and stress responses across immune and tissue compartments. This narrative review examines its relevance to autoimmune diseases, distinguishing disease-model perturbation from cellular mechanisms, human associations and contextual studies. Whole-animal Cebpd deletion supports involvement in experimental arthritis, while renal studies reveal contrasting effects across inflammatory and fibrotic models. Evidence in other autoimmune settings varies in experimental scope. Protective findings in intestinal epithelium, pancreatic β cells and psoriasis-related systems challenge a uniform inhibitory strategy. We propose a framework linking C/EBPδ activation, transcriptional programme selection and functional consequences: expression alone does not determine whether its activity is pathogenic or protective. Therapeutic development requires demonstrated target dependency, selective engagement and delivery, and assessment of protective and host-defence functions. The review identifies priorities for testing C/EBPδ as a context-dependent candidate target rather than an established treatment across autoimmune diseases.
Aberrant immune cell activation contributes to autoimmune onset and progression, where emerging evidence demonstrates a critical role for NLRP3 inflammasome activation in this context. NOD-, LRR-, and pyrin domain-containing protein 3 (NLRP3) is a well-known innate pattern recognition receptor (PRR) that is also expressed in adaptive immune cells. Two steps are required for full inflammasome activation: priming and activation. Following NLRP3 activation, caspase-1 cleaves pro-IL-1β and pro-IL-18, leading to their secretion, creating a pro-inflammatory milieu that can enhance the onset and progression of autoimmune diseases. Moreover, NLRP3 activation drives immune cells toward an inflammatory phenotype. Discovering the precise role of the NLRP3 inflammasome in immune cells opens a new avenue for treating autoimmune diseases. This review highlights the function of the NLRP3 inflammasome in innate and adaptive immune cells in the context of autoimmune disorders and discusses therapeutic targeting strategies, emphasizing areas for future research.
Objective This study aimed to compare the overall incidence and arterial-venous distribution of thrombosis, identify independent predictors of total and subtype-specific events, develop a prediction model, and evaluate the discriminative performance of risk factors in systemic lupus erythematosus (SLE) and primary Sjögren's syndrome (pSS). Methods This retrospective study included 955 SLE patients and 558 pSS patients from a single center. Cox proportional hazards regression was used to determine independent risk factors for thrombosis. Discriminative ability was assessed using the time-dependent area under the curve (AUC) and Harrell's concordance index (C-index). Results Median follow-up was 10 years (interquartile range [IQR] 8-12) for SLE and 9 years (IQR 7-12) for pSS. In multivariable analysis, independent risk factors for total thrombosis in SLE were hypertension (hazard ratio [HR] 1.523, 95% confidence interval [CI] 1.213-2.135, P = 0.03), lupus nephritis (HR 1.822, 95% CI 1.225-2.883, P < 0.0001), smoking history (HR 3.613, 95% CI 2.426-4.631, P < 0.0001), and positive lupus anticoagulant (LA) (HR 3.213, 95% CI 2.311-4.157, P < 0.0001); for pSS, they were diabetes (HR 1.913, 95% CI 1.112-3.245, P = 0.023), elevated platelet count (HR 3.115, 95% CI 1.672-6.779, P = 0.006), and positive LA (HR 2.611, 95% CI 1.697-3.782, P < 0.0001). The SLE prediction model yielded a C-index of 0.752 (95% CI 0.71-0.79), with 3-, 5-, and 10-year time-dependent AUCs of 0.778, 0.761, and 0.755. Beyond conventional discriminative metrics, positive likelihood ratio (LR+) and negative likelihood ratio (LR−) were calculated to evaluate the clinical practicality of the prediction models. In pSS, the combined discriminative capacity was limited, with a C-index of 0.665 (95% CI 0.587-0.743) and corresponding AUCs of 0.600, 0.606, and 0.639. Conclusion The underlying risk-factor profiles differ fundamentally between SLE and pSS. The SLE prediction model demonstrates acceptable-good discriminative performance and may serve as a guide for thrombotic risk stratification. Routine LA screening, alongside standardized management of modifiable cardiovascular risk factors, should be incorporated into long-term thromboprophylaxis strategies for both diseases.
