Background/Purpose: Systemic lupus erythematosus (SLE) is an autoimmune disease with a wide range of clinical manifestations. Production of autoantibodies is a hallmark of SLE and has been shown to contribute to disease pathogenesis as well as specific clinical manifestations such as nephritis. Despite the importance of autoantibodies in SLE, only a limited number of autoantibodies have been characterized and are utilized as lupus biomarkers, and many of these are not specific for lupus. We sought to address the question of whether broad autoantibody specificity profiling could identify novel and more specific autoantibodies to identify SLE patients, and if certain autoantibody specificities were enriched in patients exhibiting an interferon-I (IFN-I) signature.

Methods: To address this question, we carried out an unbiased analysis using the ProtoArray® platform (detection of >9400 autoantibodies), comparing five racially and ethnically diverse cohorts containing patients of African American, European, and Chinese descent (total of 131 healthy and 193 SLE patients).

Results: Each cohort had a group of SLE patients exhibiting very high autoantibody signals, a group that had moderate signal, and a group that had low signal against most of the 9400 autoantigens. The majority of healthy patients had very low autoantibody signals. Furthermore, we identified a core set of 17 autoantibodies that were significantly upregulated (FC>2, FDR<0.01) in SLE patients compared to healthy patients across all five cohorts. The levels of these core autoantibodies remained longitudinally stable over a 12-week period. We also demonstrated that the expression of these 17 autoantibodies correlated with levels of an interferon (IFN) signature present in whole blood from these patients.

Conclusion: Despite the diverse set of patients in our study, we were able to identify a small set of core autoantibodies that were commonly upregulated in SLE patients in all five cohorts. Importantly, we demonstrate that autoantibodies could be vital in patient stratification or as a biomarker of SLE, as our study reveals that levels of autoantibodies are potentially linked with IFN-I gene signatures.

ACR Meeting Abstracts - https://acrabstracts.org/abstract/broad-autoantibody-profiling-in-ethnically-diverse-sle-cohorts-reveals-a-set-of-conserved-autoantibodies-that-are-correlated-to-a-type-i-interferon-signature/