Allelic and copy-number variations of FcγRs affect granulocyte function and susceptibility for autoimmune blistering diseases

German AIBD Genetic Study Group, Andreas Recke*, Gestur Vidarsson, Ralf J. Ludwig, Miriam Freitag, Steffen Möller, Reinhard Vonthein, Julia Schellenberger, Ozan Haase, Siegfried Görg, Almut Nebel, Friederike Flachsbart, Stefan Schreiber, Wolfgang Lieb, Regine Gläser, Sandrine Benoit, Miklós Sárdy, Rüdiger Eming, Michael Hertl, Detlef ZillikensInke R. König, Enno Schmidt, Saleh Ibrahim, Georg Däschlein, Mattias Goebeler, Steven Goetze, Claudia Günther, Eva Hadaschik, Bernhard Homey, Nicolas Hunzelmann, Andreas Kreuter, Manfred Kunz, Undine Lippert, Wiebke Ludwig-Peitsch, Claudia Pföhler, MiklósSárdy, Michael Sticherling, Margitta Worm

*Corresponding author for this work
7 Citations (Scopus)


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.

Original languageEnglish
JournalJournal of Autoimmunity
Pages (from-to)36-44
Number of pages9
Publication statusPublished - 01.01.2015


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