The p.Arg435His Variation of IgG3 With High Affinity to FcRn Is Associated With Susceptibility for Pemphigus Vulgaris-Analysis of Four Different Ethnic Cohorts

Recke A, Konitzer S, Lemcke S, Freitag M, Sommer NM, Abdelhady M, Amoli MM, Benoit S, El-Chennawy F, Eldarouti M, Eming R, Glaeser R, Günther C, Hadaschik E, Homey B, Lieb W, Peitsch WK, Pfoehler C, Robati RM, Saeedi M, Sardy M, Sticherling M, Uzun S, Worm M, Zillikens D, Ibrahim S, Vidarsson G, Schmidt E (2018)

Publication Type: Journal article

Publication year: 2018

Journal

Book Volume: 9

DOI: 10.3389/fimmu.2018.01788

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.

Authors with CRIS profile

Involved external institutions

Universität zu Lübeck Germany (DE) Cairo University Egypt (EG) Tehran University of Medical Sciences (TUMS) / دانشگاه علوم پزشکی تهران Iran, Islamic Republic of (IR) Universitätsklinikum Würzburg Germany (DE) Mansoura University / جامعة المنصورة Egypt (EG) Philipps-Universität Marburg Germany (DE) Christian-Albrechts-Universität zu Kiel Germany (DE) Heinrich-Heine-Universität Düsseldorf Germany (DE) Ruprecht-Karls-Universität Heidelberg Germany (DE) Universität des Saarlandes (UdS) Germany (DE) Shahid Beheshti University of Medical Sciences Iran, Islamic Republic of (IR) Ludwig-Maximilians-Universität (LMU) Germany (DE) Akdeniz University Turkey (TR) Charité - Universitätsmedizin Berlin Germany (DE) Sanquin Diagnostic Services B.V. Netherlands (NL) Universitätsklinikum Carl Gustav Carus Dresden Germany (DE)

How to cite

APA:

Recke, A., Konitzer, S., Lemcke, S., Freitag, M., Sommer, N.M., Abdelhady, M.,... Schmidt, E. (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. Frontiers in Immunology, 9. https://doi.org/10.3389/fimmu.2018.01788

MLA:

Recke, Andreas, et al. "The p.Arg435His Variation of IgG3 With High Affinity to FcRn Is Associated With Susceptibility for Pemphigus Vulgaris-Analysis of Four Different Ethnic Cohorts." Frontiers in Immunology 9 (2018).

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