Anti-myeloperoxidase IgM B cells in anti-neutrophil cytoplasmic antibody-associated vasculitis

Wortel Cm, R. Wetering, Stork Em, T. Kissel, S. Reijm, D. Woude, Schie Ka, Trouw La, Teng Yko, A. Rutgers, P. Heeringa, Voll Re, M. Rizzi, N. Venhoff, Toes Rem and Scherer Hu ()
Additional contact information
Wortel Cm: Leiden University Medical Center
R. Wetering: Leiden University Medical Center
Stork Em: Leiden University Medical Center
T. Kissel: Leiden University Medical Center
S. Reijm: Leiden University Medical Center
D. Woude: Leiden University Medical Center
Schie Ka: Leiden University Medical Center
Trouw La: Leiden University Medical Center
Teng Yko: Leiden University Medical Center
A. Rutgers: University Medical Center Groningen
P. Heeringa: University Medical Center Groningen
Voll Re: University of Freiburg
M. Rizzi: University of Freiburg
Toes Rem: Leiden University Medical Center
Scherer Hu: Leiden University Medical Center

Nature Communications, 2025, vol. 16, issue 1, 1-13

Abstract: Abstract Anti-neutrophil cytoplasmic antibody (ANCA)-associated vasculitis (AAV) is a prototypic autoimmune disease, with a subset of AAV patients manifesting anti-myeloperoxidase (MPO) IgG. Patients with AAV respond positively to B cell-targeting and complement-targeting therapies, but disease flares are not uncommon. Here, by comparing samples from healthy individuals and MPO+ AVV patients, we show that B cell autoreactivity against MPO in the circulation of patients is dominated by CD27+IgM+ B cells whereas MPO-specific IgG+ cells are infrequent. Additionally, while naive anti-MPO-IgM B cells are present in both patients and controls and produce anti-MPO IgM upon stimulation, anti-MPO-IgM memory B cells and serum anti-MPO IgM are features of patients. Our results thus hint that defective elimination of B cell reactivity to MPO in the human repertoire, the presence of activated IgM+ anti-MPO B cells in disease, and a dominant role for anti-MPO IgM in complement activation, may all contribute to MPO+ AAV etiology and thereby serve as potential target for therapy.

Date: 2025
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DOI: 10.1038/s41467-025-56786-x

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