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

Author

Listed:
  • CM Wortel

    (Leiden University Medical Center)

  • R. Wetering

    (Leiden University Medical Center)

  • EM Stork

    (Leiden University Medical Center)

  • T. Kissel

    (Leiden University Medical Center)

  • S. Reijm

    (Leiden University Medical Center)

  • D. Woude

    (Leiden University Medical Center)

  • KA Schie

    (Leiden University Medical Center)

  • LA Trouw

    (Leiden University Medical Center)

  • YKO Teng

    (Leiden University Medical Center)

  • A. Rutgers

    (University Medical Center Groningen)

  • P. Heeringa

    (University Medical Center Groningen)

  • RE Voll

    (University of Freiburg
    University of Freiburg)

  • M. Rizzi

    (University of Freiburg
    University of Freiburg
    University of Freiburg
    Medical University of Vienna)

  • N. Venhoff
  • REM Toes

    (Leiden University Medical Center)

  • HU Scherer

    (Leiden University Medical Center)

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.

Suggested Citation

  • CM Wortel & R. Wetering & EM Stork & T. Kissel & S. Reijm & D. Woude & KA Schie & LA Trouw & YKO Teng & A. Rutgers & P. Heeringa & RE Voll & M. Rizzi & N. Venhoff & REM Toes & HU Scherer, 2025. "Anti-myeloperoxidase IgM B cells in anti-neutrophil cytoplasmic antibody-associated vasculitis," Nature Communications, Nature, vol. 16(1), pages 1-13, December.
    • Handle: RePEc:nat:natcom:v:16:y:2025:i:1:d:10.1038_s41467-025-56786-x
    DOI: 10.1038/s41467-025-56786-x
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    1. Matthew C. Woodruff & Richard P. Ramonell & Natalie S. Haddad & Fabliha A. Anam & Mark E. Rudolph & Tiffany A. Walker & Alexander D. Truong & Adviteeya N. Dixit & Jenny E. Han & Monica Cabrera-Mora & , 2022. "Dysregulated naive B cells and de novo autoreactivity in severe COVID-19," Nature, Nature, vol. 611(7934), pages 139-147, November.
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