AB0152 Clustered Autoantibody Reactivity Profiles and Definition of Homogeneous Systemic Lupus Erythematosus (SLE) Patient Groups

Background 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 utilize overall reactivities, co-prevalence and similarities of autoantibody reactivities in SLE patients. Such measures are expected to generate homogeneous SLE-subgroups which may represent common underlying pathophysiologies with different response to medicines and hence orffer improved medical care options. Objectives Here, we describe the development of a multiplexed autoantibody assay incorporating over 40 known SLE-antigens plus novel human protein antigens derived from large scale autoantibody screening in SLE and other autoimmune diseases such as rheumatoid arthritis, systemic sclerosis and healthy controls, The resulting assay is intendedto comprehensively analyse 87 autoantibodies in SLE patients for disease subgroupd formation. Methods A Luminex bead-based autoantibody assay was designed by combining traditional with novel biomarkers. Antigens were selected to be used for a) the diagnosis and b) differential diagnosis of SLE, have previously been linked to c) disease activity, and d) specific organ involvement, are encoded by e) 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 controls (n=1000), and autoimmune disease samples (n=500). Results Based on the individual marker pattern, we defined an autoantibody reactivity score and four SLE patient clusters (C1-C4) including patients: C1: with a higher disease activity score, broad and homogeneous autoantibody reactivity; C2: with broad, but heterogeneous autoantibody reactivity; C3) who have few autoantibodies and C4) with unusual autoantibody pattern. Conclusions High content autoantibody profiling of SLE patients reveals relevant differences in autoantibody reactivities both in amount of total reactivity as well as towards autoantibody clusters indicating specific pathophysiologies. Although more studies are needed, our findings suggest that SLE patients can be stratified into distinct, homogenous subgroups. This might be useful in clinical studies to increase the probability of successful drug development. Disclosure of Interest P. Schulz-Knappe Employee of: Protagen AG, P. Budde Employee of: Protagen AG, H. Goehler Employee of: Protagen AG, H.-D. Zucht Employee of: Protagen AG, M. Schneider: None declared, S. Vordenbaumen: None declared