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Differentiating naturally occurring and disease associated autoantibodies in MPO-ANCA vasculitis through immunogenomic and epitope comparisons

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 region 3 (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.

ORGANISM(S): Homo sapiens

PROVIDER: GSE326295 | GEO | 2026/04/17

REPOSITORIES: GEO

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