Background/Purpose: First degree relatives (FDRs) of SLE patients have an increased risk of developing autoantibodies and/or autoimmune disorders. Between 20% and 40% of FDRs develop autoimmune diseases. FDRs with a family history of SLE have 6 fold higher risk of developing SLE and a 4 fold higher risk for developing a non-SLE autoimmune disease. Previous studies have estimated that about 30% of FDRs develop anti-nuclear antibodies (ANA). This study is the first to examine the prevalence of autoimmune disease and autoantibody development in a large, multi-racial group of FDRs of lupus patients.

Methods: Clinical and demographic (age, sex, and self-reported race) information from individuals in the Lupus Family Registry and Repository was obtained for 1,092 FDRs of SLE patients, including information regarding diagnosed autoimmune disorders and symptoms of clinical autoimmune rheumatic diseases by connective tissue disease screening questionnaire (CSQ). Serum samples from European-American (EA, n=680), African-American (AA, n=264), and Hispanic (Hisp, n=148) individuals were examined for 13 common autoimmune rheumatic disease autoantibodies using a multiplexed bead-based assay. Autoantibody prevalence and association with non-SLE rheumatic disease and non-rheumatic disease was evaluated using Fisher’s exact tests and Kruskal-Wallis tests for continuous data.

Results: Among the 403 families included in the study, 134 reported autoimmune disease in FDRs (33%). In the 1092 FDRs, 172 (15.8%) reported a rheumatic autoimmune disease while 65 (5.96%) reported a non-rheumatic autoimmune disease. The most common autoimmune disease reported was rheumatoid arthritis (RA, n= 83, 7.6% of FDR). No ethnic differences were observed in the development of non-lupus autoimmune disorders in FDRs. ANA positivity was detected in 34.3% EA, 37.1% AA, and 32.4% Hisp FDRs out of all FDRs tested. Anti-Sm/nRNP antibodies were more prevalent in African-American FDRs with a rheumatic autoimmune disease (p<0.05) compared to EA and Hisp individuals with rheumatic autoimmune disease. Anti-nRNP A antibodies are significantly increased in EA FDRs with a rheumatic autoimmune disease compared to a EA FDRs with a non-rheumatic autoimmune disease or no autoimmune disease.  Anti-chromatin, Sm, Sm/nRNP, and 60kD Ro antibodies trend towards being increased in AA FDRs with a non-lupus rheumatic autoimmune disease compared to AA individuals with a non-rheumatic autoimmune disease or no autoimmune disease. In Hisp FDRs, antibodies against chromatin, nRNP A, and 60kd Ro are significantly more prevalent (p<0.05) in Hisp FDRs with

Conclusion: First degree blood relatives of SLE patients have an increased risk for developing autoimmune disease and autoantibodies. In this large, multi-racial cohort, 21.7% of the FDRs report a non-SLE autoimmune disease and about 30% have detectible ANA. Racial differences in autoantibody prevalence are observed in FDRs of lupus patients with autoantibodies against chromatin, 60kD Ro, and Sm/nRNP being the most common autoantibody specificities.

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ACR Meeting Abstracts - https://acrabstracts.org/abstract/concurrent-autoimmune-disease-and-autoantibodies-in-a-large-multi-racial-cohort-of-first-degree-blood-relatives-of-sle-patients/