Rheumatoid factor IgM autoantibodies control IgG homeostasis
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 f...
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| Format: | Article |
| Language: | English |
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Frontiers Media S.A.
2022-10-01
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| Series: | Frontiers in Immunology |
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| Online Access: | https://www.frontiersin.org/articles/10.3389/fimmu.2022.1016263/full |
| _version_ | 1797975521132281856 |
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| author | Antonella Nicolò Timm Amendt Omar El Ayoubi Marc Young Stephanie Finzel Makbule Senel Reinhard E. Voll Hassan Jumaa |
| author_facet | Antonella Nicolò Timm Amendt Omar El Ayoubi Marc Young Stephanie Finzel Makbule Senel Reinhard E. Voll Hassan Jumaa |
| author_sort | Antonella Nicolò |
| collection | DOAJ |
| description | 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. |
| first_indexed | 2024-04-11T04:36:53Z |
| format | Article |
| id | doaj.art-6859fa3d505e4ce3bf14bb6b4b83ddae |
| institution | Directory Open Access Journal |
| issn | 1664-3224 |
| language | English |
| last_indexed | 2024-04-11T04:36:53Z |
| publishDate | 2022-10-01 |
| publisher | Frontiers Media S.A. |
| record_format | Article |
| series | Frontiers in Immunology |
| spelling | doaj.art-6859fa3d505e4ce3bf14bb6b4b83ddae2022-12-28T11:24:49ZengFrontiers Media S.A.Frontiers in Immunology1664-32242022-10-011310.3389/fimmu.2022.10162631016263Rheumatoid factor IgM autoantibodies control IgG homeostasisAntonella Nicolò0Timm Amendt1Omar El Ayoubi2Marc Young3Stephanie Finzel4Makbule Senel5Reinhard E. Voll6Hassan Jumaa7Institute of Immunology, Ulm University Medical Center, Ulm, GermanyInstitute of Immunology, Ulm University Medical Center, Ulm, GermanyInstitute of Immunology, Ulm University Medical Center, Ulm, GermanyInstitute of Immunology, Ulm University Medical Center, Ulm, GermanyDepartment of Rheumatology and Clinical Immunology, University Medical Center Freiburg, Freiburg, GermanyDepartment of Neurology, Ulm University Medical Center, Ulm, GermanyDepartment of Rheumatology and Clinical Immunology, University Medical Center Freiburg, Freiburg, GermanyInstitute of Immunology, Ulm University Medical Center, Ulm, GermanyRheumatoid 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.https://www.frontiersin.org/articles/10.3389/fimmu.2022.1016263/fullautoantibodiesrheumatoid factoraffinityhomeostasisautoimmunity |
| spellingShingle | Antonella Nicolò Timm Amendt Omar El Ayoubi Marc Young Stephanie Finzel Makbule Senel Reinhard E. Voll Hassan Jumaa Rheumatoid factor IgM autoantibodies control IgG homeostasis Frontiers in Immunology autoantibodies rheumatoid factor affinity homeostasis autoimmunity |
| title | Rheumatoid factor IgM autoantibodies control IgG homeostasis |
| title_full | Rheumatoid factor IgM autoantibodies control IgG homeostasis |
| title_fullStr | Rheumatoid factor IgM autoantibodies control IgG homeostasis |
| title_full_unstemmed | Rheumatoid factor IgM autoantibodies control IgG homeostasis |
| title_short | Rheumatoid factor IgM autoantibodies control IgG homeostasis |
| title_sort | rheumatoid factor igm autoantibodies control igg homeostasis |
| topic | autoantibodies rheumatoid factor affinity homeostasis autoimmunity |
| url | https://www.frontiersin.org/articles/10.3389/fimmu.2022.1016263/full |
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