Background/Purpose:  Identifying populations at risk of SLE is essential to curtail inflammatory damage and select individuals for prevention trials. Blood relatives (Rel) of lupus patients have an increased risk of developing SLE, but no markers which identify individuals at highest risk are known. Using a large resource of SLE patients, lupus relatives, and unrelated controls, this study seeks to identify questionnaire responses and serologic factors that distinguish Rel from SLE patients and unrelated, unaffected individuals.

Methods:  This study examined European-American (EA) (n=50) and African-American (AA) (n=50) individuals with medical record-confirmed, classified SLE matched 1:1 by race and gender to unaffected Rel (n=100) and unrelated, unaffected controls (Ctls, n=100). Study 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 by bead-based assays and for 52 soluble mediators (BLyS, APRIL, cytokines, chemokines, and shed TNF receptors) by multiplexed bead-based assays or ELISA.

Results: EA SLE patients had more photosensitivity (p=0.035), with AA SLE patients having more discoid rash (p=0.028) and nephritis (p=0.045). Only 45% of Rel were positive for ANA (by IIF > 1:120) compared to 99% of SLE patients (p<0.001) and 21% of Ctls (p=0.001). Compared to Rel, Ctls had significantly lower SLE-CSQ scores (p=0.001), while SLE patients had significantly higher SLE-CSQ scores (p<0.001). Irrespective of race, a strong correlation exists between SLE-CSQ scores, number of ACR criteria, and number of autoantibody specificities (p<0.001) across Rel vs. SLE patients and Ctls. In addition, a number of soluble mediators strongly correlated with these 3 variables, including TNF superfamily members BLyS, TNFRI, and TNFRII, IFN-associated chemokines IP-10, MCP-1, and MIG, soluble receptor IL-2Rα, SCF, and IL-10 (p≤0.002 for each mediator). In certain cases, levels of soluble mediators in Rel demonstrated up-regulation similar to SLE or intermediate between SLE and Ctls. Levels of MCP-1 and MIG were similar between Rel and SLE patients, and higher than Ctls (p≤0.004), while levels of BLyS and IL-2Rα were similar between Rel and Ctls, and significantly lower than SLE patients (p<0.001). Rel had intermediate levels of TNFRI, TNFRII, IP-10, and SCF between SLE patients (p≤0.01) and Ctls (p≤0.03). In contrast, Rel had significantly higher levels of the regulatory mediator IL-10 than SLE patients (p<0.001). All soluble mediator findings were independent of race, except for TNFRI (EA>AA SLE patients, p<0.001) and TNFRII (AA>EA SLE patients, p<0.001).

Conclusion:  Lupus Rel are distinguished from SLE patients and Ctls by inflammatory mediators that correlate with SLE-specific CSQ scores, with increased levels of the regulatory mediator, IL-10, compared to SLE patients. 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.

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ACR Meeting Abstracts - https://acrabstracts.org/abstract/unaffected-lupus-relatives-are-distinguished-from-sle-patients-and-unaffected-individuals-not-related-to-sle-patients-by-lupus-specific-connective-tissue-disease-questionnaire-scores-autoantibodies/