Clinical, serological, and targeted genetic analysis of systemic lupus erythematosus in Kazakhstan

BackgroundSystemic lupus erythematosus (SLE) is a multisystem autoimmune disease characterized by the production of various antibodies and immune complex-mediated injury. Limited information exists about Kazakh patients, a heterogeneous group with different clinical manifestations and potentially unique genetic basis.ObjectiveTo describe the clinical features, associated autoantibody and cytokine profile, and the frequency of rare variants in a limited panel of genes.MethodThis study enrolled 43 Kazakh individuals: 25 with SLE and 18 healthy controls. Disease activity was assessed using the SLEDAI-2K score. Laboratory tests included C3 and C4 complement components, interleukin (IL)-6, IL-5, IL-10, IL-18, IFN and antiphospholipid IgG/IgM identified by ELISA. The antinuclear factor (ANF) on HEp-2 cells was detected using indirect immunofluorescence. Specific autoantibodies were identified by immunoblotting. A custom AmpliSeq panel of 120 genes was used on the Ion Proton Sequencer.ResultsSLE patients (SLEDAI-2K = 11,48 ± 8,7) demonstrated skin lesions (88%), joint involvement (84%), lupus nephritis (56%), and hematological disorders (40% patients). Cardiac and vascular injury was each observed in 36% of patients, while involvement of nervous system, mucous membranes, and thyroid gland each occurred in 8% of cases. Immunological tests revealed positive ANF in the majority of patients (92%) with anti-dsDNA, nucleosomes, Smith, SS-A/Ro52, SS-A/Ro60, U1-snRNP, and Rib-P0 antibodies. IL-6, IL-18, IFN levels were markedly elevated in patients with SLE relative to controls (p = .02), reflecting enhanced systemic inflammatory activity. Elevated IL-10 was found as well in patients with SLE relative to controls (p = .02). According to the results of gene panel sequencing, the most significant variants were found in genes SAMD9L, REL, IRAK1, PTPRC, TLR7, TNFAIP3, IL6ST, BLK, CCR5, TFPI, CLEC16 A, IL2RB, ITGA2B, ABCC2, KIF5A, NCF2, and CD5, none of which showed statistically important enrichment in the disease cohort.ConclusionAnalysis of data obtained from Kazakh patients with SLE revealed diverse autoimmune profiles, including various antibodies, pro- and anti-inflammatory cytokines, as well as several variants in REL, IRAK1, PTRPC, IL6ST genes. The findings presented may contribute to the development of personalized diagnostic tools for predicting disease trajectories and guiding treatment decisions.