ORIGINAL RESEARCH article
Front. Med.
Sec. Rheumatology
Differentiating naturally occurring and disease associated autoantibodies in MPO-ANCA vasculitis through immunogenomic and epitope comparisons
Dhruti Chen 1,2
Dhruti Chen 1,3
Bridget A. Peck 2
Justin J. Taylor 4
Ismael Gomez-Martinez 2
Mark G. Woodcock 2,1
Benjamin Garrett Vincent 2
Ronald Falk 2
John S. Poulton 2
Donna O'Dell Bunch 2
1. University of North Carolina Hospitals, Chapel Hill, United States
2. The University of North Carolina at Chapel Hill, Chapel Hill, United States
3. The University of North Carolina at Chapel Hill School of Medicine, Chapel Hill, United States
4. University of Virginia, Charlottesville, United States
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Abstract
It has been established that there are naturally occurring autoantibodies including ANCAs that are found in healthy individuals. While ANCAs are pathogenic in patients with vasculitis, they can be present without active clinical disease. This raises the question of what is distinct about the autoantibodies which cause disease. We used highly sensitive methods to isolate autoantibody producing cells from healthy individuals and patients with MPO-ANCA to sequence the BCRs (autoantibodies). We also used serum samples to analyze the reactive epitopes from both groups. We found that the isolated autoantigen specific B cells from our patients (but not healthy individuals) produced high levels of detectable MPO-ANCAs. The BCRs from patient cells showed clonal expansion and significant overlap in the complementarity determining region3 (CDR3). We also identified distinct epitopes bound by patient autoantibodies only. Our study highlights the differences in naturally occurring autoantibodies (from healthy individuals) compared to autoantibodies identified in patients with MPO-ANCA.
Summary
Keywords
ANCA vasculitis, Autoantibodies, epitope, MPO, PR3
Received
09 January 2026
Accepted
20 February 2026
Copyright
© 2026 Chen, Chen, Peck, Taylor, Gomez-Martinez, Woodcock, Vincent, Falk, Poulton and Bunch. This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) or licensor are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.
*Correspondence: Dhruti Chen; Dhruti Chen
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