Evaluating the autoantibody reactome in giant cell arteritis
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Objective
To determine whether autoantibodies are present in giant cell arteritis (GCA) using a high-dimensional autoantibody array.
Methods
Serum was collected from patients with GCA (n=20), other related vascular inflammatory diseases (Takayasu arteritis n=12, IgG4-RD n=5, Behcet’s disease n=6), SLE (n=5) and healthy controls (n=12). Autoantibodies to 15,312 protein targets were measured using the GeneCopeia OmicsArray™ proteomic antigen microarray panel.
Results
Differential abundance analysis revealed no autoantibodies significantly elevated in GCA or other related vascular inflammatory diseases. In contrast, the SLE group showed a strong and promiscuous autoantibody response, with 175 significantly associated autoantibodies (Benjamini-Hochberg-adjusted P <0.05).
Conclusions
No autoantibodies were significantly elevated in GCA. We identified known and novel autoantibodies in SLE
Key messages
What is already known on the topic?
There is circumstantial evidence for a role of B cells in the pathogenesis of GCA. Immunohistochemical and spatial transcriptomic studies have identified B cells and plasma cells in GCA-affected arteries. Genetic studies have identified an association with the HLA class II region. Two small studies have reported autoantibodies in GCA, but these findings have not been independently validated. To date, no GCA-specific antibodies have been translated into clinical practice.
What this study adds?
- Our study does not support previous reports suggesting that circulating autoantibodies are commonly observed in GCA.
- We identify known autoantibodies in SLE, providing evidence of platform validity, and in addition identify novel autoantibodies.
- We showcase a rigorous permutation-based method to evaluate whether autoantibody positivity based on thresholds derived from healthy controls in the context of high-dimensional arrays reflects the play of chance.
How this study might affect research practice or policy?
- Our findings suggest that circulating autoantibodies are unlikely to be a clinically useful diagnostic in GCA.
- Further research examining roles for B cells in GCA pathogenesis independent of autoantibody production is needed.
- Future research should evaluate the newly identified SLE-associated antibodies in terms of their role in pathogenesis and their clinical utility as biomarkers of disease activity and prognosis.
