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01-02-2019 | Original Article

Immunological features and functional analysis of anti-CFH autoantibodies in patients with atypical hemolytic uremic syndrome

Authors: Wei-yi Guo, Di Song, Xiao-rong Liu, Zhi Chen, Hui-jie Xiao, Jie Ding, Shu-zhen Sun, Hong-yan Liu, Su-xia Wang, Feng Yu, Ming-hui Zhao, On behalf of the Chinese Renal-TMA Network

Published in: Pediatric Nephrology | Issue 2/2019

Abstract

Objective

Atypical hemolytic uremic syndrome (aHUS) is associated with defective complement regulation. Anti-complement factor H (CFH) antibodies were thought to participate in the pathogenesis of aHUS. The aim of this study was to address the functions and properties of CFH autoantibodies in a Chinese Han cohort of aHUS patients.

Methods

Thirty-six anti-CFH antibody-positive aHUS patients at the acute phase of the disease were involved in this study. Clinical data of the patients were collected. Anti-CFH immunoglobulin G (IgG) subclasses and antibody isotypes were detected by ELISA. Epitope mapping was performed using recombinant CFH fragments (SCRs 1–4, SCR 7, SCRs 11–14, and SCRs 19–20). Purified IgG from plasma from seven patients were used for functional analyses.

Results

All patients presented with the classic triad of HUS. The anti-CFH autoantibodies mostly bound to the SCRs 19–20 domains of CFH but not the SCRs 1–4 domains. CFI cofactor activity was not disturbed by the anti-CFH antibody in any of the seven patients. Purified IgG interfered with the binding of CFH to C3b and CFH-mediated sheep erythrocyte protection in all seven patients. IgG from 4/5 (80%) patients tested inhibited the binding of CFH to glomerular endothelial cells.

Conclusions

Our study suggests that the properties of CFH antibodies from patients with aHUS, including the recognition of SCRs and IgG subclasses, can influence and impair the biological role of CFH and therefore contribute to aHUS susceptibility.

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Title: Immunological features and functional analysis of anti-CFH autoantibodies in patients with atypical hemolytic uremic syndrome
Authors: Wei-yi Guo
Di Song
Xiao-rong Liu
Zhi Chen
Hui-jie Xiao
Jie Ding
Shu-zhen Sun
Hong-yan Liu
Su-xia Wang
Feng Yu
Ming-hui Zhao
On behalf of the Chinese Renal-TMA Network
Publication date: 01-02-2019
Publisher: Springer Berlin Heidelberg
Published in: Pediatric Nephrology / Issue 2/2019
Print ISSN: 0931-041X
Electronic ISSN: 1432-198X
DOI: https://doi.org/10.1007/s00467-018-4074-4

Keynote webinar | Spotlight on sleep in brain health

Springer Medicine

Immunological features and functional analysis of anti-CFH autoantibodies in patients with atypical hemolytic uremic syndrome

Abstract

Objective

Methods

Results

Conclusions

Keynote webinar | Spotlight on sleep in brain health

Springer Medicine

Abstract

Objective

Methods

Results

Conclusions

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