Frontiers in Immunology (Aug 2018)
The p.Arg435His Variation of IgG3 With High Affinity to FcRn Is Associated With Susceptibility for Pemphigus Vulgaris—Analysis of Four Different Ethnic Cohorts
- Andreas Recke,
- Andreas Recke,
- Sarah Konitzer,
- Susanne Lemcke,
- Miriam Freitag,
- Nele Maxi Sommer,
- Mohammad Abdelhady,
- Mahsa M. Amoli,
- Sandrine Benoit,
- Farha El-Chennawy,
- Mohammad Eldarouti,
- Rüdiger Eming,
- Regine Gläser,
- Claudia Günther,
- Eva Hadaschik,
- Bernhard Homey,
- Wolfgang Lieb,
- Wolfgang Lieb,
- Wiebke K. Peitsch,
- Wiebke K. Peitsch,
- Claudia Pföhler,
- Reza M. Robati,
- Marjan Saeedi,
- Miklós Sárdy,
- Michael Sticherling,
- Soner Uzun,
- Margitta Worm,
- Detlef Zillikens,
- Saleh Ibrahim,
- Gestur Vidarsson,
- Enno Schmidt,
- the German AIBD Genetic Study Group,
- Alexander Kreuter,
- Christos C. Zouboulis,
- Georg Däschlein,
- Kerstin Steinbrink,
- Manfred Kunz,
- Nicolas Hunzelmann,
- Steven Goetze
Affiliations
- Andreas Recke
- Lübeck Institute of Experimental Dermatology (LIED), University of Lübeck, Lübeck, Germany
- Andreas Recke
- Department of Dermatology, Allergology and Venereology, University of Lübeck, Lübeck, Germany
- Sarah Konitzer
- Lübeck Institute of Experimental Dermatology (LIED), University of Lübeck, Lübeck, Germany
- Susanne Lemcke
- Lübeck Institute of Experimental Dermatology (LIED), University of Lübeck, Lübeck, Germany
- Miriam Freitag
- Lübeck Institute of Experimental Dermatology (LIED), University of Lübeck, Lübeck, Germany
- Nele Maxi Sommer
- Lübeck Institute of Experimental Dermatology (LIED), University of Lübeck, Lübeck, Germany
- Mohammad Abdelhady
- Department of Dermatology, Faculty of Medicine, Cairo University, Giza, Egypt
- Mahsa M. Amoli
- Metabolic Disorders Research Center, Endocrinology and Metabolism Molecular – Cellular Sciences Institute, Tehran University of Medical Sciences, Tehran, Iran
- Sandrine Benoit
- Department of Dermatology, Venereology and Allergology, University Hospital Würzburg, Würzburg, Germany
- Farha El-Chennawy
- Department of Clinical Pathology, Mansoura Faculty of Medicine, Mansoura University, Mansoura, Egypt
- Mohammad Eldarouti
- Department of Dermatology, Faculty of Medicine, Cairo University, Giza, Egypt
- Rüdiger Eming
- Department of Dermatology and Allergology, Phillips-Universität Marburg, Marburg, Germany
- Regine Gläser
- Department of Dermatology, Venereology and Allergology, Christian Albrecht University, Kiel, Germany
- Claudia Günther
- Department of Dermatology, University Hospital of Dresden, Dresden, Germany
- Eva Hadaschik
- 0Department of Dermatology, Ruprecht-Karls-University of Heidelberg, Heidelberg, Germany
- Bernhard Homey
- 1Department of Dermatology, Heinrich Heine University, Düsseldorf, Germany
- Wolfgang Lieb
- 2Institute of Epidemiology, Christian-Albrechts-University, Kiel, Germany
- Wolfgang Lieb
- 3Popgen Biobank, Christian-Albrechts-University, Kiel, Germany
- Wiebke K. Peitsch
- 4Department of Dermatology, University Medical Center Mannheim, Heidelberg University, Mannheim, Germany
- Wiebke K. Peitsch
- 5Department of Dermatology, Vivantes Klinikum im Friedrichshain, Berlin, Germany
- Claudia Pföhler
- 6Department of Dermatology, Saarland University Medical School, Homburg/Saar, Germany
- Reza M. Robati
- 7Skin Research Center, Shahid Beheshti University of Medical Sciences, Tehran, Iran
- Marjan Saeedi
- 7Skin Research Center, Shahid Beheshti University of Medical Sciences, Tehran, Iran
- Miklós Sárdy
- 8Department of Dermatology, Ludwig Maximilian University Munich, Munich, Germany
- Michael Sticherling
- 9Department of Dermatology, University of Erlangen-Nuremberg, Erlangen, Germany
- Soner Uzun
- 0Department of Dermatology, Faculty of Medicine, Akdeniz University, Antalya, Turkey
- Margitta Worm
- 1Department of Dermatology, Venerology and Allergology, Allergy Center Charité, Charité-Medical University Berlin, Berlin, Germany
- Detlef Zillikens
- Department of Dermatology, Allergology and Venereology, University of Lübeck, Lübeck, Germany
- Saleh Ibrahim
- Lübeck Institute of Experimental Dermatology (LIED), University of Lübeck, Lübeck, Germany
- Gestur Vidarsson
- 2Department of Experimental Hematology, Sanquin Research Institute, Amsterdam, Netherlands
- Enno Schmidt
- Lübeck Institute of Experimental Dermatology (LIED), University of Lübeck, Lübeck, Germany
- the German AIBD Genetic Study Group
- Alexander Kreuter
- Christos C. Zouboulis
- Georg Däschlein
- Kerstin Steinbrink
- Manfred Kunz
- Nicolas Hunzelmann
- Steven Goetze
- DOI
- https://doi.org/10.3389/fimmu.2018.01788
- Journal volume & issue
-
Vol. 9
Abstract
IgG3 is the IgG subclass with the strongest effector functions among all four IgG subclasses and the highest degree of allelic variability among all constant immunoglobulin genes. Due to its genetic position, IgG3 is often the first isotype an antibody switches to before IgG1 or IgG4. Compared with the other IgG subclasses, it has a reduced half-life which is probably connected to a decreased affinity to the neonatal Fc receptor (FcRn). However, a few allelic variants harbor an amino acid replacement of His435 to Arg that reverts the half-life of the resulting IgG3 to the same level as the other IgG subclasses. Because of its functional impact, we hypothesized that the p.Arg435His variation could be associated with susceptibility to autoantibody-mediated diseases like pemphigus vulgaris (PV) and bullous pemphigoid (BP). Using a set of samples from German, Turkish, Egyptian, and Iranian patients and controls, we were able to demonstrate a genetic association of the p.Arg435His variation with PV risk, but not with BP risk. Our results suggest a hitherto unknown role for the function of IgG3 in the pathogenesis of PV.
Keywords
