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

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

Object Details

• Location: Deutsche Nationalbibliothek Frankfurt am Main
• Extent: Online-Ressource
• Language: Englisch
• Notes: Nature Communications. - 16, 1 (2025) , 1582, ISSN: 2041-1723

Classification and Topics

• Classification: Medizin, Gesundheit

Contributors, Places and Time

• Event: Veröffentlichung
• (where): Freiburg
• (who): Universität
• (when): 2025
• Creator: Wortel, Corrie M. ; van de Wetering, Renee ; Stork, Eva Maria ; Kissel, Theresa ; Reijm, Sanne ; van der Woude, Diane ; van Schie, Karin A. ; Trouw, Leendert A. ; Teng, Y. K. Onno ; Rutgers, A. ; Heeringa, Peter ; Voll, Reinhard ; Rizzi, Marta ; Venhoff, Nils ; Toes, Rene E.M ; Scherer, Hans Ulrich

Further information

• DOI: 10.1038/s41467-025-56786-x
• URN: urn:nbn:de:bsz:25-freidok-2630241
• Rights: Open Access; Der Zugriff auf das Objekt ist unbeschränkt möglich.
• Last update: 07.03.0001, 2:58 PM CET