TY - JOUR A1 - Recke, Andreas A1 - Konitzer, Sarah A1 - Lemcke, Susanne A1 - Freitag, Miriam A1 - Sommer, Nele Maxi A1 - Abdelhady, Mohammad A1 - Amoli, Mahsa M. A1 - Benoit, Sandrine A1 - El-Chennawy, Farha A1 - Eldarouti, Mohammad A1 - Eming, Rüdiger A1 - Gläser, Regine A1 - Günther, Claudia A1 - Hadaschik, Eva A1 - Homey, Bernhard A1 - Lieb, Wolfgang A1 - Peitsch, Wiebke K. A1 - Pföhler, Claudia A1 - Robati, Reza M. A1 - Saeedi, Marjan A1 - Sárdy, Miklós A1 - Sticherling, Michael A1 - Uzun, Soner A1 - Worm, Margitta A1 - Zillikens, Detlef A1 - Ibrahim, Saleh A1 - Vidarsson, Gestur A1 - Schmidt, Enno 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 JF - frontiers in Immunology 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. KW - immunology KW - dermatology KW - autoantibodies KW - allotype KW - pemphigus KW - Diagnose KW - pemphigoid KW - half-life KW - functional genetics Y1 - 2018 U6 - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-225073 VL - 9 ER - TY - JOUR A1 - Schierer, Stefan A1 - Ostalecki, Christian A1 - Zinser, Elisabeth A1 - Lamprecht, Ricarda A1 - Plosnita, Bianca A1 - Stich, Lena A1 - Doerrie, Jan A1 - Lutz, Manfred B A1 - Schuler, Gerold A1 - Baur, Andreas S T1 - Extracellular vesicles from mature dendritic cells (DC) differentiate monocytes into immature DC JF - Life Science Alliance N2 - During inflammation, murine and human monocytes can develop into dendritic cells (DC), but this process is not entirely understood. Here, we demonstrate that extracellular vesicles (EV) secreted by mature human DC (maDC) differentiate peripheral monocytes into immature DC, expressing a unique marker pattern, including 6-sulfo LacNAc (slan), Zbtb46, CD64, and CD14. While EV from both maDC and immature DC differentiated monocytes similar to GM-CSF/IL-4 stimulation, only maDC-EV produced precursors, which upon maturation stimulus developed into T-cell-activating and IL-12p70-secreting maDC. Mechanistically, maDC-EV induced cell signaling through GM-CSF, which was abundant in EV as were IL-4 and other cytokines and chemokines. When injected into the mouse skin, murine maDC-EV attracted immune cells including monocytes that developed activation markers typical for inflammatory cells. Skin-injected EV also reached lymph nodes, causing a similar immune cell infiltration. We conclude that DC-derived EV likely serve to perpetuate an immune reaction and may contribute to chronic inflammation. KW - medical research KW - immunology Y1 - 2018 U6 - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-228587 VL - 1 IS - 6 ER -