TY - JOUR
T1 - The p.Arg435His Variation of IgG3 With High Affinity to FcRn Is Associated With Susceptibility for Pemphigus Vulgaris-Analysis of Four Different Ethnic Cohorts
AU - German AIBD Genetic Study Group
AU - Recke, Andreas
AU - Konitzer, Sarah
AU - Lemcke, Susanne
AU - Freitag, Miriam
AU - Sommer, Nele Maxi
AU - Abdelhady, Mohammad
AU - Amoli, Mahsa M
AU - Benoit, Sandrine
AU - El-Chennawy, Farha
AU - Eldarouti, Mohammad
AU - Eming, Rüdiger
AU - Gläser, Regine
AU - Günther, Claudia
AU - Hadaschik, Eva
AU - Homey, Bernhard
AU - Lieb, Wolfgang
AU - Peitsch, Wiebke K
AU - Pföhler, Claudia
AU - Robati, Reza M
AU - Saeedi, Marjan
AU - Sárdy, Miklós
AU - Sticherling, Michael
AU - Uzun, Soner
AU - Worm, Margitta
AU - Zillikens, Detlef
AU - Ibrahim, Saleh
AU - Vidarsson, Gestur
AU - Schmidt, Enno
PY - 2018
Y1 - 2018
N2 - 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.
AB - 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.
U2 - 10.3389/fimmu.2018.01788
DO - 10.3389/fimmu.2018.01788
M3 - Journal articles
C2 - 30116249
VL - 9
SP - 1788
JO - Frontiers in Immunology
JF - Frontiers in Immunology
ER -
