Case Report : Severe Complement-Mediated Thrombotic Microangiopathy in IgG4-Related Disease Secondary to Anti-Factor H IgG4 Autoantibodies
Copyright © 2021 Breville, Zamberg, Sadallah, Stephan, Ponte and Seebach..
Objective: To first describe and estimate the potential pathogenic role of Ig4 autoantibodies in complement-mediated thrombotic microangiopathy (TMA) in a patient with IgG4-related disease (IgG4-RD).
Methods: This study is a case report presenting a retrospective review of the patient's medical chart. Plasma complement C3 and C4 levels, immunoglobulin isotypes and subclasses were determined by nephelometry, the complement pathways' activity (CH50, AP50, MBL) using WIESLAB® Complement System assays. Human complement factor H levels, anti-complement factor H auto-antibodies were analyzed by ELISA, using HRP-labeled secondary antibodies specific for human IgG, IgG4, and IgA, respectively. Genetic analyses were performed by exome sequencing of 14 gens implicated in complement disorders, as well as multiplex ligation-dependent probe amplification looking specifically for CFH, CFHR1-2-3, and 5.
Results: Our brief report presents the first case of IgG4-RD with complement-mediated TMA originating from both pathogenic CFHR 1 and CFHR 4 genes deletions, and inhibitory anti-complement factor H autoantibodies of the IgG4 subclass. Remission was achieved with plasmaphereses, corticosteroids, and cyclophosphamide. Following remission, the patient was diagnosed with lymphocytic meningitis and SARS-CoV-2 pneumonia with an uneventful recovery.
Conclusion: IgG4-RD can be associated with pathogenic IgG4 autoantibodies. Genetic predisposition such as CFHR1 and CFHR4 gene deletions enhance the susceptibility to the formation of inhibitory anti-Factor H IgG4 antibodies.
| Medienart: |
E-Artikel |
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| Erscheinungsjahr: |
2020 |
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| Erschienen: |
2020 |
| Enthalten in: |
Zur Gesamtaufnahme - volume:11 |
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| Enthalten in: |
Frontiers in immunology - 11(2020) vom: 01., Seite 604759 |
| Sprache: |
Englisch |
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| Beteiligte Personen: |
Breville, Gautier [VerfasserIn] |
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| Links: |
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| Anmerkungen: |
Date Completed 10.03.2021 Date Revised 10.03.2021 published: Electronic-eCollection Citation Status MEDLINE |
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| doi: |
10.3389/fimmu.2020.604759 |
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| funding: |
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| Förderinstitution / Projekttitel: |
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| PPN (Katalog-ID): |
NLM322011582 |
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| 100 | 1 | |a Breville, Gautier |e verfasserin |4 aut | |
| 245 | 1 | 0 | |a Case Report |b Severe Complement-Mediated Thrombotic Microangiopathy in IgG4-Related Disease Secondary to Anti-Factor H IgG4 Autoantibodies |
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| 500 | |a Date Revised 10.03.2021 | ||
| 500 | |a published: Electronic-eCollection | ||
| 500 | |a Citation Status MEDLINE | ||
| 520 | |a Copyright © 2021 Breville, Zamberg, Sadallah, Stephan, Ponte and Seebach. | ||
| 520 | |a Objective: To first describe and estimate the potential pathogenic role of Ig4 autoantibodies in complement-mediated thrombotic microangiopathy (TMA) in a patient with IgG4-related disease (IgG4-RD) | ||
| 520 | |a Methods: This study is a case report presenting a retrospective review of the patient's medical chart. Plasma complement C3 and C4 levels, immunoglobulin isotypes and subclasses were determined by nephelometry, the complement pathways' activity (CH50, AP50, MBL) using WIESLAB® Complement System assays. Human complement factor H levels, anti-complement factor H auto-antibodies were analyzed by ELISA, using HRP-labeled secondary antibodies specific for human IgG, IgG4, and IgA, respectively. Genetic analyses were performed by exome sequencing of 14 gens implicated in complement disorders, as well as multiplex ligation-dependent probe amplification looking specifically for CFH, CFHR1-2-3, and 5 | ||
| 520 | |a Results: Our brief report presents the first case of IgG4-RD with complement-mediated TMA originating from both pathogenic CFHR 1 and CFHR 4 genes deletions, and inhibitory anti-complement factor H autoantibodies of the IgG4 subclass. Remission was achieved with plasmaphereses, corticosteroids, and cyclophosphamide. Following remission, the patient was diagnosed with lymphocytic meningitis and SARS-CoV-2 pneumonia with an uneventful recovery | ||
| 520 | |a Conclusion: IgG4-RD can be associated with pathogenic IgG4 autoantibodies. Genetic predisposition such as CFHR1 and CFHR4 gene deletions enhance the susceptibility to the formation of inhibitory anti-Factor H IgG4 antibodies | ||
| 650 | 4 | |a Case Reports | |
| 650 | 4 | |a IgG4-related disease | |
| 650 | 4 | |a SARS CoV2 | |
| 650 | 4 | |a anti-factor H auto-antibodies | |
| 650 | 4 | |a antibodies | |
| 650 | 4 | |a atypical hemolytic uremic syndrome | |
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| 650 | 4 | |a thrombotic microangiopathy | |
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| 650 | 7 | |a Complement C3b Inactivator Proteins |2 NLM | |
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| 700 | 1 | |a Stephan, Caroline |e verfasserin |4 aut | |
| 700 | 1 | |a Ponte, Belen |e verfasserin |4 aut | |
| 700 | 1 | |a Seebach, Jörg D |e verfasserin |4 aut | |
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