Journal article
Defective complement control of Factor H (Y402H) and FHL-1 in age-related macular degeneration
Molecular immunology, Vol.44(13), pp.3398-3406
2007
DOI: 10.1016/j.molimm.2007.02.012
PMID: 17399790
Abstract
The common variant in the human complement Factor H gene (CFH), with Tyr402His, is linked to age-related macular degeneration (AMD), a prevalent disorder leading to visual impairment and irreversible blindness in elderly patients. Here we show that the risk variant CFH 402His displays reduced binding to C reactive protein (CRP), heparin and retinal pigment epithelial cells. This reduced binding can cause inefficient complement regulation at the cell surface, particularly when CRP is recruited to injured sites and tissue. In addition, we identify the Factor H-like protein 1 (FHL-1), an alternative splice product of the
CFH gene as an additional protein that includes the risk residue 402, and thus confers risk for AMD. FHL-1 is expressed in the eye and the FHL-1 402His risk variant shows similar reduced cell binding and likely reduced complement regulatory functions on the cell surface. CFH and FHL-1 may act in concert in the eye and the reduced surface binding may result in inappropriate local complement control, which in turn can lead to inflammation, disturbance of local physiological homeostasis and progression to cell damage. As a consequence, these processes may lead to AMD pathogenesis.
Details
- Title: Subtitle
- Defective complement control of Factor H (Y402H) and FHL-1 in age-related macular degeneration
- Creators
- Christine Skerka - Department of Infection Biology, Leibniz Institute for Natural Products Research and Infection Biology, Hans Knöll Institute, Jena, GermanyNadine Lauer - Department of Infection Biology, Leibniz Institute for Natural Products Research and Infection Biology, Hans Knöll Institute, Jena, GermanyAndreas A.W.A Weinberger - Department of Ophthalmology, RWTH Aachen University, Aachen, GermanyClaudia N Keilhauer - Department of Ophthalmology, University of Würzburg, Würzburg, GermanyJürgen Sühnel - Biocomputing group, Leibniz Institute for Age Research, Fritz Lipmann Institute, Jena, GermanyRichard Smith - Carver College of Medicine, The University of Iowa, Iowa City, USAUrsula Schlötzer–Schrehardt - Department of Ophthalmology, University of Erlangen-Nürnberg, Erlangen, GermanyLars Fritsche - Institute of Human Genetics, University of Regensburg, GermanyStefan Heinen - Department of Infection Biology, Leibniz Institute for Natural Products Research and Infection Biology, Hans Knöll Institute, Jena, GermanyAndrea Hartmann - Department of Infection Biology, Leibniz Institute for Natural Products Research and Infection Biology, Hans Knöll Institute, Jena, GermanyBernhard H.F Weber - Institute of Human Genetics, University of Regensburg, GermanyPeter F Zipfel - Department of Infection Biology, Leibniz Institute for Natural Products Research and Infection Biology, Hans Knöll Institute, Jena, Germany
- Resource Type
- Journal article
- Publication Details
- Molecular immunology, Vol.44(13), pp.3398-3406
- DOI
- 10.1016/j.molimm.2007.02.012
- PMID
- 17399790
- NLM abbreviation
- Mol Immunol
- ISSN
- 0161-5890
- eISSN
- 1872-9142
- Publisher
- Elsevier Ltd
- Language
- English
- Date published
- 2007
- Academic Unit
- Roy J. Carver Department of Biomedical Engineering; Molecular Physiology and Biophysics; Anatomy and Cell Biology; Stead Family Department of Pediatrics; Iowa Neuroscience Institute; Otolaryngology; Internal Medicine
- Record Identifier
- 9984006315402771
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