Autoimmune Crossroads Revisited: A Systematic Review and Meta-Analysis of Molecular Pathogenesis in Rheumatoid Arthritis and Systemic Lupus Erythem<i>atosus</i>

Background: According to their aetiology, RA and SLE are both autoimmune diseases that share similarities in their molecular manifestations and the immunological responses. Objective: This study aimed to review and measure the molecular evidence that connects systemic lupus erythematosus and rheumatoid arthritis. Methods: According to the PRISMA 2020 guidelines, a systematic review and a meta-analysis were carried out. Up until February 2025, searches were conducted in Web of Science, PubMed, Embase, and Scopus. Original studies that reported concurrent molecular-level data on RA and SLE were among the eligible studies. Using RoB 2.0, ROBINS-I, and modified criteria for in silico research, two reviewers independently carried out screening, data extraction, and risk of bias assessment. A random-effects meta-analysis and narrative synthesis were used to combine the data. I2 statistics were utilised to assess heterogeneity. The GRADE framework was used to evaluate the evidence's certainty. Results: Ten of the 120 identified studies were included that contained more than 58,000 participants. Common molecular characteristics included the transcriptional regulators like GATA1 and PBX1, as well as the dysregulation of the PI3K, MAPK, and interferon pathways. There was moderate heterogeneity (I2 ≈58%) and a pooled odds ratio of 3.0 (95% CI: 2.1–4.2) for the shared molecular marker association. Evidence certainty ranged from moderate to high. Conclusion: There was a great deal of molecular overlap between RA and SLE, especially in immune signalling and transcriptional regulation. Researchers can develop shared biomarkers and treatments that complement precision autoimmune medical techniques thanks to these shared characteristics.