Background/Purpose: In SLE, early diagnosis, differentiation to other autoimmune diseases and prognostic stratification are still great challenges. Hence, SLE represents an enormous challenge for the clinical development of effective therapies.Detecting a broad set of SLE-associated autoantibodies might help to investigate the number, co-prevalence and similarities of autoantibody reactivities in SLE patients. Here, we describe the development of a multiplexed autoantibody assay, which enables the comprehensive analysis of 87 autoantibodies in SLE patients

Methods: A Luminex bead-based autoantibody assay was designed by combining traditional with novel antigens. Autoantibodies were selected to be used for the a) diagnosis and b) differential diagnosis of SLE; have previously been linked to c) disease activity, and d) specific organ involvement; e) react with proteins encoded by  interferon type I response genes; and f) may have utility for patient subgrouping. Autoantibody reactivity against these antigens was tested in over 700 SLE, healthy control (n=1000), and autoimmune disease samples (n=500).

Results: Based on the individual marker pattern, patients either belong to clusters defined by characteristic markers, or are phenotypically more overlapping with other autoimmune diseases. The analysis of the autoantibody reactivity yields at least four different reactivity groups (G1-G4) including patients: G1: with a higher disease activity score, broad and homogeneous autoantibody reactivity; G2: with broad, but heterogeneous autoantibody reactivity; G3) who have few autoantibodies and G4) with unusual autoantibody pattern.

Conclusion: The multiplexed analysis of autoantibodies in SLE enables defining an autoantibody reactivity score and SLE patient clusters. This might support the stratification of SLE patients into more homogenous subgroups in clinical studies thereby increasing the probability of successful drug development.

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ACR Meeting Abstracts - https://acrabstracts.org/abstract/identification-of-homogeneous-systemic-lupus-erythematosus-sle-patient-groups-using-clustered-autoantibody-reactivities/