Distinct impact of IgG subclass on autoantibody pathogenicity in different IgG4-mediated diseases
© 2022, Bi et al..
IgG4 is the least potent human IgG subclass for the FcγR-mediated antibody effector function. Paradoxically, IgG4 is also the dominant IgG subclass of pathogenic autoantibodies in IgG4-mediated diseases. Here, we show that the IgG subclass and Fc-FcγR interaction have a distinct impact on the pathogenic function of autoantibodies in different IgG4-mediated diseases in mouse models. While IgG4 and its weak Fc-FcγR interaction have an ameliorative role in the pathogenicity of anti-ADAMTS13 autoantibodies isolated from thrombotic thrombocytopenic purpura (TTP) patients, they have an unexpected exacerbating effect on anti-Dsg1 autoantibody pathogenicity in pemphigus foliaceus (PF) models. Strikingly, a non-pathogenic anti-Dsg1 antibody variant optimized for FcγR-mediated effector function can attenuate the skin lesions induced by pathogenic anti-Dsg1 antibodies by promoting the clearance of dead keratinocytes. These studies suggest that IgG effector function contributes to the clearance of autoantibody-Ag complexes, which is harmful in TTP, but beneficial in PF and may provide new therapeutic opportunity.
| Medienart: |
E-Artikel |
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| Erscheinungsjahr: |
2022 |
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| Erschienen: |
2022 |
| Enthalten in: |
Zur Gesamtaufnahme - volume:11 |
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| Enthalten in: |
eLife - 11(2022) vom: 03. Aug. |
| Sprache: |
Englisch |
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| Beteiligte Personen: |
Bi, Yanxia [VerfasserIn] |
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| Links: |
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| Themen: |
ADAMTS13 |
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| Anmerkungen: |
Date Completed 19.08.2022 Date Revised 07.09.2022 published: Electronic Citation Status MEDLINE |
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| doi: |
10.7554/eLife.76223 |
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| funding: |
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| Förderinstitution / Projekttitel: |
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| PPN (Katalog-ID): |
NLM344401987 |
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| 245 | 1 | 0 | |a Distinct impact of IgG subclass on autoantibody pathogenicity in different IgG4-mediated diseases |
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| 520 | |a IgG4 is the least potent human IgG subclass for the FcγR-mediated antibody effector function. Paradoxically, IgG4 is also the dominant IgG subclass of pathogenic autoantibodies in IgG4-mediated diseases. Here, we show that the IgG subclass and Fc-FcγR interaction have a distinct impact on the pathogenic function of autoantibodies in different IgG4-mediated diseases in mouse models. While IgG4 and its weak Fc-FcγR interaction have an ameliorative role in the pathogenicity of anti-ADAMTS13 autoantibodies isolated from thrombotic thrombocytopenic purpura (TTP) patients, they have an unexpected exacerbating effect on anti-Dsg1 autoantibody pathogenicity in pemphigus foliaceus (PF) models. Strikingly, a non-pathogenic anti-Dsg1 antibody variant optimized for FcγR-mediated effector function can attenuate the skin lesions induced by pathogenic anti-Dsg1 antibodies by promoting the clearance of dead keratinocytes. These studies suggest that IgG effector function contributes to the clearance of autoantibody-Ag complexes, which is harmful in TTP, but beneficial in PF and may provide new therapeutic opportunity | ||
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| 700 | 1 | |a Zhou, Shengru |e verfasserin |4 aut | |
| 700 | 1 | |a Zhao, Yingjie |e verfasserin |4 aut | |
| 700 | 1 | |a Zhang, Yan |e verfasserin |4 aut | |
| 700 | 1 | |a Zhang, Huihui |e verfasserin |4 aut | |
| 700 | 1 | |a Liu, Mingdong |e verfasserin |4 aut | |
| 700 | 1 | |a Zhou, Aiwu |e verfasserin |4 aut | |
| 700 | 1 | |a Xu, Jianrong |e verfasserin |4 aut | |
| 700 | 1 | |a Pan, Meng |e verfasserin |4 aut | |
| 700 | 1 | |a Zhao, Yiming |e verfasserin |4 aut | |
| 700 | 1 | |a Li, Fubin |e verfasserin |4 aut | |
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