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<p>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<sup>+</sup> AVV patients, we show that B cell autoreactivity against MPO in the circulation of patients is dominated by CD27<sup>+</sup>IgM<sup>+</sup> B cells whereas MPO-specific IgG<sup>+</sup> 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<sup>+</sup> anti-MPO B cells in disease, and a dominant role for anti-MPO IgM in complement activation, may all contribute to MPO<sup>+</sup> AAV etiology and thereby serve as potential target for therapy.</p>

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

  • 期刊论文

  • 出版模式：

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  • 发表日期：

    2025年2月12日

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  • CM Wortel,
  • R. van de Wetering,
  • EM Stork,
  • T. Kissel,
  • S. Reijm,
  • D. van der Woude,
  • KA van Schie,
  • LA Trouw,
  • YKO Teng,
  • A. Rutgers,
  • P. Heeringa,
  • RE Voll,
  • M. Rizzi,
  • N. Venhoff,
  • REM Toes,
  • HU Scherer

摘要

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.