MICRORNA-MEDIATED REGULATION OF IMMUNE RESPONSES: MOLECULAR INSIGHTS INTO AUTOIMMUNE DISORDERS

Abstract

Background: Autoimmune disorders (AIDs) represent a heterogeneous group of diseases characterized by aberrant immune activation and the loss of self-tolerance, leading to chronic tissue inflammation and organ damage. Emerging evidence highlights the regulatory role of microRNAs (miRNAs) in modulating immune cell differentiation, cytokine signaling, and antigen presentation, thereby influencing the pathogenesis and progression of AIDs. Aims and Objectives: This study aimed to evaluate the role of miRNAs in the immunopathogenesis of AIDs among the Lahore Pakistani community. Methodology: This retrospective cross-sectional study was conducted in Govt. Teaching Hospital, Shahdra, Lahore, a tertiary care hospital of Lahore, Pakistan, between August 2022 and July 2025. Peripheral blood samples from 110 clinically diagnosed AID patients in which we include systemic lupus erythematosus and rheumatoid arthritis and 50 age- and sex-matched healthy controls were subjected to molecular profiling. Quantitative reverse-transcription polymerase chain reaction (qRT-PCR) was employed to evaluate the expression levels of candidate miRNAs (miR-21, miR-146a, miR-155, and miR-181a). Bioinformatics analyses were applied to predict target gene networks, while statistical modeling determined associations between miRNA dysregulation and clinical disease severity scores. Results & Findings: Compared with controls, patients demonstrated significant upregulation of miR-21 (3.4-fold, p<0.001) and miR-155 (2.7-fold, p<0.01), whereas miR-146a and miR-181a exhibited downregulation (−2.1-fold and −1.8-fold, respectively; p<0.05). Notably, altered expression of miR-21 correlated positively with elevated serum TNF-α and IL-6 levels (r=0.68, p<0.001), while decreased miR-146a expression strongly associated with higher disease activity indices (r=−0.52, p<0.01). Network analysis identified critical regulatory axes linking these miRNAs to NF-κB and JAK/STAT signaling pathways. Conclusion: The study underscores the pivotal role of miRNA-mediated regulation in shaping immune responses in autoimmune disorders within the Pakistani population. Distinct miRNA signatures may serve as potential diagnostic biomarkers and therapeutic targets, offering molecular insights into personalized disease management strategies. These findings contribute to global efforts to elucidate epigenetic mechanisms underpinning autoimmunity and support the integration of miRNA-based diagnostics.