Immunogenetic Landscape of Secondary Sjögren’s Syndrome in Systemic Sclerosis and Lupus Erythematosus: Insights from Kazakhstan

<b>Background:</b> Secondary Sjögren’s syndrome (sSS) frequently develops in patients systemic autoimmune diseases such as systemic lupus erythematosus (SLE) and systemic sclerosis (SSc). Nevertheless, its immunogenetic features remain poorly understood, particularly in underrepresented populations.<br /> <b>Objective: </b>To investigate the immunological and genetic characteristics of secondary Sjögren’s syndrome in Kazakh patients diagnosed with SSc and SLE.<br /> <b>Methods: </b>Patients diagnosed with sSS associated with SLE and SSc were enrolled in the study. SLEDAI-2K and the modified Rodnan skin score were measured, respectively. Antinuclear factor on HEp-2 cells was analyzed by indirect immunofluorescence; autoantibody profiles were determined by immunoblotting. Interleukin (IL)-6 levels were measured by ELISA. Whole-exome sequencing was performed using a targeted panel of autoimmune-related genes. Variants were analyzed and clustered using Ion Reporter software.<br /> <b>Results: </b>Antinuclear factor on Hep2 cells was positive in all SLE-sSS and 75% of SSc-sSS cases. SS-A/Ro60 and SS-A/Ro52 antibodies were frequently detected in both SLE-sSS and SSc-sSS patients, whereas SS-B antibodies were less common. Complement levels were mostly within normal ranges despite 2 SSc-sSS patients. One patient in the SSc group showed an elevated IL-6. Genetic analysis revealed likely pathogenic variants in SAMD9L, ABCC2, IL6ST, and TNFAIP3 in sSS patients.<br /> <b>Conclusion:</b> This study provides insight into the immunogenetic features of secondary Sjögren’s syndrome in Kazakh patients, suggesting overlapping genetic patterns in sSS among both SSc and SLE groups. Limitations include the small sample size and cross-sectional design, which limits generalizability, but provide a foundation for further larger-scale research integrating longitudinal follow-up and comprehensive genomic profiling.