Identifying populations at risk of SLE is essential to curtail inflammatory damage and implement prevention strategies. Using unique participant resources, this study examined an initial cohort of previously unaffected blood relatives who transitioned to classified SLE (n=45), plus a confirmatory cohort of European-American (EA) (n=50) and African-American (AA) (n=50) SLE patients, matched by race and gender to unaffected relatives (n=190) and unrelated healthy controls (Ctls, n=145). Participants provided clinical and demographic information, and completed the SLE-specific portion of the CTD Screening Questionnaire (SLE-CSQ). Plasma samples were assessed for autoantibody production and for 52 soluble mediators by multiplexed bead-based assays or ELISA. In both cohorts, compared to unaffected relatives, Ctls had significantly lower (p=0.001), while SLE patients had significantly higher (p≤0.001), SLE-CSQ scores. Irrespective of race, a strong correlation existed between SLE-CSQ scores, number of ACR criteria, and number of autoantibody specificities (p≤0.001). A strong correlation was noted between these three aforementioned variables and select soluble mediators, including TNF superfamily member BLyS, pro-inflammatory mediator stem cell factor (SCF), and the regulatory mediator IL-10 (p≤0.004 for each mediator), among others. Levels of BLyS in unaffected relatives and Ctls were significantly lower than SLE patients (p≤0.001). Unaffected relatives had intermediate levels of SCF between SLE patients (p≤0.01) and Ctls (p≤0.03). In contrast, unaffected relatives had significantly higher levels of the regulatory mediator IL-10 than SLE patients (p≤0.001). Identification of factors which discern unaffected lupus relatives from SLE patients may be beneficial to identify potential treatments to curtail inflammatory damage for prevention trials.
Cincinnati Children’s Hospital Medical Center and US Department of Veterans Affairs Medical Center
Oklahoma Medical Research Foundation and Oklahoma University Health Sciences Center