OP0101 B CELL POLYGENIC RISK SCORES ASSOCIATED WITH ANTI-DSDNA ANTIBODIES AND NEPHRITIS IN SYSTEMIC LUPUS ERYTHEMATOSUS

Background Lupus nephritis (LN) is one of the main clinical challenges in systemic lupus erythematosus (SLE) and a cause significant morbidity mortality. Genetic contribution to SLE pathogenesis important, genetic profiling through polygenic risk scores has been shown useful stratify patients according dominating molecular disease mechanism. [1] This not, however, investigated for specific manifestations. Objectives In this work, we aimed investigate associations between B cell (PRSs) manifestations SLE. Methods Female with (n = 1248) healthy control individuals 519) were genotyped using Illumina’s Global Screening Array. Two PRSs calculated [2] , including 20 GWS loci genes assigned B-cell related pathways KEGG, GO Reactome databases, subset 12 these limited activation pathways. defined as high highest quartile low 1-3, groups compared by logistic regression (SPSS, version 28.0.1.0). HLA variants HLA-DRB1*03:01 HLA-DRB1*15:01 assessed tag SNPs. A p-value < 0.05 was considered significant. Results more prevalent PRS (OR 1.84 (1.42-2.38), p=4.0×10 -6 ) mean higher cases than controls, 2.92 (2.88-2.96) 2.68 (2.63-2.74) p 4.1 × 10 -11 ). Immunologic disorder (ACR -82) dsDNA antibodies among 1.44 (1.08-1.93), p=1.4×10 -2 OR 1.47 (1.07-2.01), p=1.8×10 immunologic antibodies, respectively). Also, effect sizes augmented serotypes HLA-DRB1*15:01, prevalence (87 %) demonstrated HLA-DRB1*03/15 +/+ combined 1.64 (1.06-2.54), 0.028, vs PRS), Figure 1. Anti-dsDNA associated class III or IV 4.66 (2.78-7.80), p=5.2×10 -9) ACR-82 criteria 1.32 (1.00-1.74), 0.048). Numerically, observed PRS, but difference not statistically 1.20 (0.91-1.59), 0.19). Conclusion High burden function antibody development LN. Assessing may be important order determine influencing predict phenotype. References [1]Sandling, J.K. et al. Molecular revealed gene-centred DNA sequencing. Ann Rheum Dis 80 109-117 (2021). [2]Reid, S. score early onset, damage accrual decreased survival erythematosus. 79 363-369 (2020). Associations (ACR-82) anti-dsDNA subgroups. stratified into three HLA-type (positive (DRB1*03/15 +/- -/+), positive both +/+) negative -/-) variants). Each group then divided two based on patients’ (highest 1-3). Prevalence ACR -82 (A) (B) all 6 groups. ACR, American College Rheumatology; dsDNA, double-stranded DNA; HLA, human leukocyte antigen; SLE, erythematosus; SNP, single nucleotide polymorphism; score. Acknowledgements: NIL. Disclosure Interests None Declared.