Rheumatoid factor IgM autoantibodies control IgG homeostasis

Abstract: Rheumatoid arthritis is an autoimmune disease characterized by joint inflammation due to autoantibodies targeting multiple self-proteins. Most patients with poor prognosis show elevated titers of IgM antibodies specifically binding to IgG. Such autoreactive antibodies are referred to as rheumatoid factor (RF). However, their biological function and contribution to disease progression remains elusive. We have recently shown that autoreactive antibodies are present in healthy individuals and play an important role in regulating physiological processes. This regulatory mechanism is determined by the class and affinity of the autoreactive antibody, as low-affinity autoreactive IgM neutralizes the recognized autoantigen while high-affinity IgM protects its autoantigen from degradation. Here, we show that RFs possessing a high affinity and mono-specificity to IgG have a stabilizing effect on IgG, whereas low-affinity polyreactive RFs neutralize IgG in vivo. These results suggest that autoreactive IgM antibodies recognizing IgG play a crucial role in regulating IgG homeostasis and that a disbalance between IgM-mediated IgG degradation and stabilization might affect the onset and progression of autoimmune diseases. Consequently, restoring this balance using low-affinity anti-IgG IgM might be a promising therapeutic approach for autoimmune diseases involving autoreactive IgG

Standort
Deutsche Nationalbibliothek Frankfurt am Main
Umfang
Online-Ressource
Sprache
Englisch
Anmerkungen
Frontiers in immunology. - 13 (2022) , 1016263, ISSN: 1664-3224

Ereignis
Veröffentlichung
(wo)
Freiburg
(wer)
Universität
(wann)
2022
Urheber
Nicolò, Antonella
Amendt, Timm
El Ayoubi, Omal
Young, Marc
Finzel, Stephanie
Şenel, Makbule
Voll, Reinhard
Jumaa, Hassan

DOI
10.3389/fimmu.2022.1016263
URN
urn:nbn:de:bsz:25-freidok-2311197
Rechteinformation
Open Access; Der Zugriff auf das Objekt ist unbeschränkt möglich.
Letzte Aktualisierung
15.08.2025, 07:23 MESZ

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  • 2022

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