Journal article
Factor H Autoantibodies and Complement-Mediated Diseases
Frontiers in immunology, Vol.11, pp.607211-607211
2020
DOI: 10.3389/fimmu.2020.607211
PMCID: PMC7770156
PMID: 33384694
Abstract
Factor H (FH), a member of the regulators-of-complement-activation (RCA) family of proteins, circulates in human plasma at concentrations of 180-420 mg/L where it controls the alternative pathway (AP) of complement in the fluid phase and on cell surfaces. When the regulatory function of FH is impaired, complement-mediated tissue injury and inflammation occur, leading to diseases such as atypical hemolytic uremic syndrome (a thrombotic microangiopathy or TMA), C3 glomerulopathy (C3G) and monoclonal gammopathy of renal significance (MGRS). A pathophysiological cause of compromised FH function is the development of autoantibodies to various domains of the FH protein. FH autoantibodies (FHAAs) are identified in 10.9% of patients with aHUS, 3.2% of patients with C3G, and rarely in patients with MGRS. The phenotypic variability of FHAA-mediated disease reflects both the complexity of FH and the epitope specificity of FHAA for select regions of the native protein. In this paper, we have characterized FHAA epitopes in a large cohort of patients diagnosed with TMA, C3G or MGRS. We explore the epitopes recognized by FHAAs in these diseases and the association of FHAAs with the genetic deletion of both copies of the
gene to show how these disease phenotypes are associated with this diverse spectrum of autoantibodies.
Details
- Title: Subtitle
- Factor H Autoantibodies and Complement-Mediated Diseases
- Creators
- Yuzhou Zhang - University of IowaNicolo Ghiringhelli Borsa - University of IowaDingwu Shao - University of IowaArthur Dopler - Universität UlmMichael B Jones - University of IowaNicole C Meyer - University of IowaGabriella R Pitcher - University of IowaAmanda O Taylor - University of IowaCarla M Nester - University of IowaChristoph Q Schmidt - Universität UlmRichard J H Smith - University of Iowa
- Resource Type
- Journal article
- Publication Details
- Frontiers in immunology, Vol.11, pp.607211-607211
- DOI
- 10.3389/fimmu.2020.607211
- PMID
- 33384694
- PMCID
- PMC7770156
- ISSN
- 1664-3224
- eISSN
- 1664-3224
- Grant note
- R01 DK110023 / NIDDK NIH HHS
- Language
- English
- Date published
- 2020
- Academic Unit
- Roy J. Carver Department of Biomedical Engineering; Molecular Physiology and Biophysics; Anatomy and Cell Biology; Nephrology, Dialysis and Transplantation; Stead Family Department of Pediatrics; Iowa Neuroscience Institute; Otolaryngology; Internal Medicine
- Record Identifier
- 9984256843102771
Metrics
16 Record Views