Allelic and copy-number variations of FcγRs affect granulocyte function and susceptibility for autoimmune blistering diseases
Research output: Contribution to journal › Research article › Contributed › peer-review
Contributors
- Sanquin Blood Supply Foundation
- Universitätsklinikum Schleswig-Holstein - Campus Lübeck
- Kiel University
- University of Würzburg
- Ludwig Maximilian University of Munich
- University of Marburg
- University of Greifswald
- Friedrich Schiller University Jena
- Heidelberg University
- Heinrich Heine University Düsseldorf
- University of Cologne
- Ruhr University Bochum
- Leipzig University
- Dessau Medical Center
- Saarland University
- Friedrich-Alexander University Erlangen-Nürnberg
- Charité – Universitätsmedizin Berlin
- University of Lübeck
Abstract
Low-affinity Fcγ receptors (FcγR) bridge innate and adaptive immune responses. In many autoimmune diseases, these receptors act as key mediators of the pathogenic effects of autoantibodies. Genes encoding FcγR exhibit frequent variations in sequence and gene copy number that influence their functional properties. FcγR variations also affect the susceptibility to systemic autoimmunity, e.g. systemic lupus erythematosus and rheumatoid arthritis. This raises the question whether FcγR variations are also associated with organ-specific autoimmunity, particularly autoantibody-mediated diseases, such as subepidermal autoimmune blistering diseases (AIBD). A multitude of evidence suggests a pathogenic role of neutrophil granulocyte interaction with autoantibodies via FcγR. In a two-stage study, we analyzed whether the FcγR genotype affects neutrophil function and mRNA expression, and consequently, bullous pemphigoid (BP) disease risk. We compared this to findings in pemphigus vulgaris/foliaceus (PV/PF), two Fc-independent AIBDs. Our results indicate that both allele and copy number variation of FcγR genes affect FcγR mRNA expression and reactive oxygen species (ROS) release by granulocytes. Susceptibility of BP was associated with FcγR genotypes that led to a decreased ROS release by neutrophils, indicating an unexpected protective role for these cells. BP and PV/PF differed substantially regarding the FcγR genotype association patterns, pointing towards different disease etiologies.
Details
Original language | English |
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Pages (from-to) | 36-44 |
Number of pages | 9 |
Journal | Journal of autoimmunity |
Volume | 2015 |
Issue number | 61 |
Publication status | E-pub ahead of print - 29 May 2015 |
Peer-reviewed | Yes |
External IDs
PubMed | 26032265 |
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ORCID | /0000-0002-4330-1861/work/151982026 |
Keywords
ASJC Scopus subject areas
Keywords
- Autoantibodies, Autoimmune blistering dermatoses, Fcγ receptors, Functional genetics, Joint copy number and allelic variation, Neutrophils, Reactive oxygen species