Exploring genetic linkage between rheumatoid arthritis and systemic lupus erythematosus through biological networks and prioritizing omega-3 fatty acids as a potent therapeutic

Abstract

Rheumatoid arthritis (RA) and systemic lupus erythematosus (SLE) are chronic autoimmune diseases characterized by persistent inflammation and progressive tissue damage, posing significant challenges to effective treatment. To gain deeper insights into their shared molecular mechanisms, we performed an integrative bioinformatics investigation aimed at uncovering common pathways and therapeutic targets. Using a cutoff of p-value < 0.05 and Log2 FC > 1, differential gene expression analysis identified 1178 DEGs in RA and 7783 DEGs in SLE, with 358 genes common to both diseases. Construction of a protein–protein interaction network revealed several hub genes, including PDE4A, H1-10, H4C6, and PIP, which were highly interconnected and clustered into functional modules. Molecular docking analysis demonstrated that alpha linolenic acid (ALA) exhibited strong binding affinity toward these key proteins, with binding energies ranging from –8.3 to –9.4 kcal/mol. Toxicity profiling further suggested that ALA possesses a favorable safety profile, showing minimal risks of hepatotoxicity, neurotoxicity, and related adverse outcomes. Functional enrichment pointed to the involvement of common signaling cascades, particularly the cAMP and TGF-β pathways, as potential therapeutic avenues. Collectively, our findings highlight ALA as a promising therapeutic candidate capable of modulating shared molecular drivers in RA and SLE. Further in vitro and in vivo validation is essential to confirm its mechanistic effects and therapeutic potential for clinical translation.