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

TitelThe p.Arg435His Variation of IgG3 With High Affinity to FcRn Is Associated With Susceptibility for Pemphigus Vulgaris-Analysis of Four Different Ethnic Cohorts.
MedientypJournal Article
Jahr der Veröffentlichung2018
AutorenRecke A, Konitzer S, Lemcke S, Freitag M, Sommer NMaxi, Abdelhady M, Amoli MM, Benoit S, El-Chennawy F, Eldarouti M, Eming R, Gläser R, Günther C, Hadaschik E, Homey B, Lieb W, Peitsch WK, Pföhler C, Robati RM, Saeedi M, Sárdy M, Sticherling M, Uzun S, Worm M, Zillikens D, Ibrahim S, Vidarsson G, Schmidt E
Corporate AuthorsGerman AIBD Genetic Study Group
JournalFront Immunol
Volume9
Pagination1788
Datum der Veröffentlichung2018
ISSN1664-3224
Zusammenfassung

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.

DOI10.3389/fimmu.2018.01788
Alternate JournalFront Immunol
PubMed ID30116249
PubMed Central IDPMC6082936