ACTIVATION OF THE INTERFERON PATHWAY IS DEPENDENT UPON AUTOANTIBODIES IN AFRICAN AMERICAN SLE PATIENTS, BUT NOT IN EUROPEAN-AMERICAN SLE PATIENTS

Background: Lupus is a heterogeneous autoimmune disease characterized by anti-RNA-binding protein autoantibodies and high circulating levels of interferon. The disease is more prevalent and more severe in African-Americans as compared to European-Americans. Objectives: We aimed to explore how IFN-related gene expression pathways differ in patients according to their ancestry and anti-RBP profile. Methods: Whole blood from 33 female SLE patients and 16 matched controls from EA and AA ancestral backgrounds was analyzed through Affymetrix gene expression arrays, and the data were further studied through Ingenuity Pathways Analysis for canonical pathway comparison. An independent replication cohort of more than 100 SLE patient samples and 30 controls was used to test the hypotheses generated by the microarray data, using qPCR to quantify gene expression. Results: Both EA and AA patients with positive anti-RBP (RBP+) showed involvement of IFN-related canonical pathways including IFN Signaling (P = 5.8 x 10-11 and 1.3 x 10-7 respectively), and a number of pattern recognition receptor pathways. All of these pathways were also involved in EA patients with negative anti-RBP (RBP-) but they were completely absent in AA patients with RBP-. The microarray results were confirmed by a replication study through qPCR on 3 IFN-inducible genes, IFIT1, MX1 and PKR. Conclusions: Our data show that IFN-induced gene expression is completely dependent on the presence of autoantibodies in AA SLE patients but not in EA patients. Disclosure of Interest: None DeclaredCitation: , volume 72, supplement s3, year 2013, page Session: Poster Tour: Pathogenesis of Lupus and Sjögren's syndrome ( )