Background/Purpose: Autoantibodies serve as important biomarkers for diagnosing autoimmune diseases. However, current clinical assays for their detection often face challenges, such as uncertainty about the specific autoantigen or a narrow focus on well-known autoantigens, which typically results in low sensitivity and specificity. To address these limitations we have developed a multiplex antigen bead-array that enables the parallel detection of both known and novel autoantibodies. Ultimately, we aim to improve the classification and serological characterization of autoimmune diseases.

Methods: We performed proteome-wide autoantibody screenings on plasma samples from 1000 vasculitis patients, 180 patients with systemic sclerosis, as well as healthy and inflammatory controls. These screenings utilized custom antigen-arrays featuring 42,000 protein fragments (representing 17,000 unique proteins) and 2,000 full-length secreted proteins from the Human Protein Atlas. The Samples were sourced from well-characterised cohorts through collaborations with expert clinicians.

Results: In ANCA-vasculitis, we identified new candidate biomarkers associated with subgroups of patients with specific clinical features and relapse. The screening of patients with systemic sclerosis revealed novel candidate biomarkers for both the diagnosis and subclassification of patients with skin and lung fibrosis. Moreover, we generated a bead-array for accurate and parallel detection of autoantibodies targeting the well-known autoantigens Scl70/TOPO-1, Ro52/SSA/TRIM21, CENPs, MPO and PR3.

Conclusion: Our multiplex antigen-array effectively detected well-known clinically relevant autoantibodies. Combining clinical expertise with our high-throughput approach enabled the discovery of novel candidate biomarkers, which could improve patient diagnosis and subclassification. These findings underscore the potential of multiplex autoantibody assays for enhancing diagnostic precision across a range of autoimmune conditions.

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ACR Meeting Abstracts - https://acrabstracts.org/abstract/development-of-a-multi-disease-panel-for-autoimmune-diseases/