Altered soluble mediator levels and systemic lupus erythematosus-specific Connective Tissue Disease Screening Questionnaire (CSQ) scores differentiate unaffected relatives of lupus patients from healthy individuals with no family history of SLE (CCR4P.214)

Abstract

Abstract Identifying populations at risk of SLE who remain unaffected would provide insights for potential disease prevention. Using a unique resource of SLE patient family members, first degree relatives (FDRs) of SLE patients (n = 154) with plasma samples available from previous genetic studies and who remained unaffected at follow-up evaluation (mean time = 6.8 years) were matched to healthy individuals unrelated to SLE patients (Controls). FDRs and Controls provided clinical and demographic information, and completed screening questionairres at baseline (BL) and follow-up (FU). BL and FU plasma samples were assessed for autoantibody production and soluble mediators. FDRs had significantly higher BL and FU CSQ scores (p<0.0001), but no difference in the number of positive autoantibodies compared to Controls. FDRs had significant (p < 0.01) increases in 38 (of 52) soluble mediators at BL and FU, including IFN-associated chemokines, TNFR ligands, and regulatory mediators (p<0.002). Levels of MIP-1α (p=0.008), MIG (p=0.019), GROα (p=0.001), ICAM-1 (p=0.007), and VEGF (p=0.004), along with CSQ scores (p=0.010), best distinguished FDRs from Controls in logistic regression models. These alterations are present despite lack of progression to classified SLE, suggesting that multiple perturbations in immune-mediated inflammatory processes present in FDRs of SLE patients may be offset by inhibitory factors.