Soluble mediators and clinical features predict transition to systemic lupus erythematosus classification in previously unaffected relatives of SLE patients (HUM3P.243)

Abstract

Abstract Healthy relatives of lupus patients have an increased risk of developing SLE, but predictors and mechanisms of disease transition are unknown. Unaffected relatives of SLE patients (n=409) were enrolled in this follow-up study to identify factors associated with transition to SLE. Participants provided detailed demographic and clinical information, including the Connective Tissue Disease Screening Questionnaire (CSQ). Medical records were reviewed for ACR classification criteria. Plasma samples were tested for the presence of autoantibodies and soluble mediators. Forty-five relatives (11%) transitioned to classified SLE during follow-up (mean time = 6.4 years) who had more autoantibodies (p<0.0001) and higher pre-classification (baseline) CSQ scores (p<0.0001). Relatives who transitioned also had elevated baseline levels of inflammatory mediators, including BLyS, SCF, and IFN-associated chemokines (p<0.05), with concurrent decreased regulatory mediators, including TGF-β and IL-10 (p<0.05). Logistic regression analysis revealed that baseline ACR and CSQ scores (but not autoantibodies), and baseline plasma levels of SCF and TGF-β were significant and independent predictors of SLE transition. Thus, perturbations in immune-mediated processes precede SLE clinical classification and can help identify unaffected relatives at highest risk of future SLE classification for early intervention studies.