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

Lina Zaripova 1 * , Abai Baigenzhin 2, Zhanna Zhabakova 3, Alyona Boltanova 4, Maxim Solomadin 3, Natalya Krivoruchko 5, Diana Makimova 6
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1 Department of Scientific and Innovation Management, National Scientific Medical Center, Astana, Kazakhstan
2 Chairman of the Board, National Scientific Medical Center, Astana, Kazakhstan
3 Genetic Laboratory, National Scientific Medical Center, Astana, Kazakhstan
4 Central Research Laboratory, National Scientific Medical Center, Astana, Kazakhstan
5 Rheumathology Department, Mexel Health, Astana, Kazakhstan
6 Department of Internal Medicine No.4, Astana Medical University, Astana, Kazakhstan
* Corresponding Author
J CLIN MED KAZ, Volume 22, Issue 4, pp. 6-14. https://doi.org/10.23950/jcmk/16776
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Author contribution. L.Z. conceptualized the study, supervised the research process, and contributed to manuscript preparation. A.B. conceived of the presented idea. L.Z. and N.K. were responsible for patient recruitment, D.M. – for clinical data collection, A.B. and Zh.Zh. for sample processing and immune analysis. M.S. and Zh.Zh. performed the genetic analyses and bioinformatic interpretation. L.Z. and L.K. drafted the manuscript, and all authors reviewed and approved the final version.

ABSTRACT

Background: 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.
Objective: To investigate the immunological and genetic characteristics of secondary Sjögren’s syndrome in Kazakh patients diagnosed with SSc and SLE.
Methods: 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.
Results: 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.
Conclusion: 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.
Keywords: Secondary Sjögren’s Syndrome, Systemic Sclerosis, Systemic Lupus Erythematosus, Antibodies, Genetic Predisposition.

CITATION

Zaripova L, Baigenzhin A, Zhabakova Z, Boltanova A, Solomadin M, Krivoruchko N, et al. Immunogenetic Landscape of Secondary Sjögren’s Syndrome in Systemic Sclerosis and Lupus Erythematosus: Insights from Kazakhstan. J CLIN MED KAZ. 2025;22(4):6-14. https://doi.org/10.23950/jcmk/16776

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