TY - JOUR A1 - Tony, Hans-Peter A1 - Burmester, Gerd A1 - Schulze-Koops, Hendrik A1 - Grunke, Mathias A1 - Henes, Joerg A1 - Kötter, Ina A1 - Haas, Judith A1 - Unger, Leonore A1 - Lovric, Svjetlana A1 - Haubitz, Marion A1 - Fischer-Betz, Rebecca A1 - Chehab, Gamal A1 - Rubbert-Roth, Andrea A1 - Specker, Christof A1 - Weinerth, Jutta A1 - Holle, Julia A1 - Müller-Ladner, Ulf A1 - König, Ramona A1 - Fiehn, Christoph A1 - Burgwinkel, Philip A1 - Budde, Klemens A1 - Sörensen, Helmut A1 - Meurer, Michael A1 - Aringer, Martin A1 - Kieseier, Bernd A1 - Erfurt-Berge, Cornelia A1 - Sticherling, Michael A1 - Veelken, Roland A1 - Ziemann, Ulf A1 - Strutz, Frank A1 - von Wussow, Praxis A1 - Meier, Florian MP A1 - Hunzelmann, Nico A1 - Schmidt, Enno A1 - Bergner, Raoul A1 - Schwarting, Andreas A1 - Eming, Rüdiger A1 - Schwarz-Eywill, Michael A1 - Wassenberg, Siegfried A1 - Fleck, Martin A1 - Metzler, Claudia A1 - Zettl, Uwe A1 - Westphal, Jens A1 - Heitmann, Stefan A1 - Herzog, Anna L. A1 - Wiendl, Heinz A1 - Jakob, Waltraud A1 - Schmidt, Elvira A1 - Freivogel, Klaus A1 - Dörner, Thomas A1 - Hertl, Michael A1 - Stadler, Rudolf T1 - Safety and clinical outcomes of rituximab therapy in patients with different autoimmune diseases: experience from a national registry (GRAID) JF - Arthritis Research & Therapy N2 - Introduction: Evidence from a number of open-label, uncontrolled studies has suggested that rituximab may benefit patients with autoimmune diseases who are refractory to standard-of-care. The objective of this study was to evaluate the safety and clinical outcomes of rituximab in several standard-of-care-refractory autoimmune diseases (within rheumatology, nephrology, dermatology and neurology) other than rheumatoid arthritis or non-Hodgkin’s lymphoma in a real-life clinical setting. Methods: Patients who received rituximab having shown an inadequate response to standard-of-care had their safety and clinical outcomes data retrospectively analysed as part of the German Registry of Autoimmune Diseases. The main outcome measures were safety and clinical response, as judged at the discretion of the investigators. Results: A total of 370 patients (299 patient-years) with various autoimmune diseases (23.0% with systemic lupus erythematosus, 15.7% antineutrophil cytoplasmic antibody-associated granulomatous vasculitides, 15.1% multiple sclerosis and 10.0% pemphigus) from 42 centres received a mean dose of 2,440 mg of rituximab over a median (range) of 194 (180 to 1,407) days. The overall rate of serious infections was 5.3 per 100 patient-years during rituximab therapy. Opportunistic infections were infrequent across the whole study population, and mostly occurred in patients with systemic lupus erythematosus. There were 11 deaths (3.0% of patients) after rituximab treatment (mean 11.6 months after first infusion, range 0.8 to 31.3 months), with most of the deaths caused by infections. Overall (n = 293), 13.3% of patients showed no response, 45.1% showed a partial response and 41.6% showed a complete response. Responses were also reflected by reduced use of glucocorticoids and various immunosuppressives during rituximab therapy and follow-up compared with before rituximab. Rituximab generally had a positive effect on patient well-being (physician’s visual analogue scale; mean improvement from baseline of 12.1 mm) KW - GRAID Y1 - 2011 U6 - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-142856 VL - 13 IS - R75 ER - 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 - Schmidt, Enno A1 - Sticherling, Michael A1 - Sárdy, Miklós A1 - Eming, Rüdiger A1 - Goebeler, Matthias A1 - Hertl, Michael A1 - Hofmann, Silke C. A1 - Hunzelmann, Nicolas A1 - Kern, Johannes S. A1 - Kramer, Harald A1 - Nast, Alexander A1 - Orzechowski, Hans‐Dieter A1 - Pfeiffer, Christiane A1 - Schuster, Volker A1 - Sitaru, Cassian A1 - Zidane, Miriam A1 - Zillikens, Detlef A1 - Worm, Margitta T1 - S2k guidelines for the treatment of pemphigus vulgaris/foliaceus and bullous pemphigoid: 2019 update JF - JDDG: Journal der Deutschen Dermatologischen Gesellschaft KW - pemphigus vulgaris KW - pemphigus foliaceus KW - S2k guidelines Y1 - 2020 U6 - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-217806 VL - 18 IS - 5 SP - 516 EP - 526 ER - TY - JOUR A1 - Bumiller-Bini Hoch, Valéria A1 - Kohler, Ana Flávia A1 - Augusto, Danillo G. A1 - Lobo-Alves, Sara Cristina A1 - Malheiros, Danielle A1 - Cipolla, Gabriel Adelman A1 - Winter Boldt, Angelica Beate A1 - Braun-Prado, Karin A1 - Wittig, Michael A1 - Franke, Andre A1 - Pföhler, Claudia A1 - Worm, Margitta A1 - van Beek, Nina A1 - Goebeler, Matthias A1 - Sárdy, Miklós A1 - Ibrahim, Saleh A1 - Busch, Hauke A1 - Schmidt, Enno A1 - Hundt, Jennifer Elisabeth A1 - Araujo-Souza, Patrícia Savio de A1 - Petzl-Erler, Maria Luiza T1 - Genetic associations and differential mRNA expression levels of host genes suggest a viral trigger for endemic pemphigus foliaceus JF - Viruses N2 - The long search for the environmental trigger of the endemic pemphigus foliaceus (EPF, fogo selvagem) has not yet resulted in any tangible findings. Here, we searched for genetic associations and the differential expression of host genes involved in early viral infections and innate antiviral defense. Genetic variants could alter the structure, expression sites, or levels of the gene products, impacting their functions. By analyzing 3063 variants of 166 candidate genes in 227 EPF patients and 194 controls, we found 12 variants within 11 genes associated with differential susceptibility (p < 0.005) to EPF. The products of genes TRIM5, TPCN2, EIF4E, EIF4E3, NUP37, NUP50, NUP88, TPR, USP15, IRF8, and JAK1 are involved in different mechanisms of viral control, for example, the regulation of viral entry into the host cell or recognition of viral nucleic acids and proteins. Only two of nine variants were also associated in an independent German cohort of sporadic PF (75 patients, 150 controls), aligning with our hypothesis that antiviral host genes play a major role in EPF due to a specific virus–human interaction in the endemic region. Moreover, CCL5, P4HB, and APOBEC3G mRNA levels were increased (p < 0.001) in CD4+ T lymphocytes of EPF patients. Because there is limited or no evidence that these genes are involved in autoimmunity, their crucial role in antiviral responses and the associations that we observed support the hypothesis of a viral trigger for EPF, presumably a still unnoticed flavivirus. This work opens new frontiers in searching for the trigger of EPF, with the potential to advance translational research that aims for disease prevention and treatment. KW - endemic pemphigus foliaceus KW - virus KW - genetic association KW - differential gene expression KW - autoimmune disease KW - environmental factors Y1 - 2022 U6 - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-270572 SN - 1999-4915 VL - 14 IS - 5 ER - TY - JOUR A1 - Buhl, Timo A1 - Beissert, Stefan A1 - Gaffal, Evelyn A1 - Goebeler, Matthias A1 - Hertl, Michael A1 - Mauch, Cornelia A1 - Reich, Kristian A1 - Schmidt, Enno A1 - Schön, Michael P. A1 - Sticherling, Michael A1 - Sunderkötter, Cord A1 - Traidl‐Hoffmann, Claudia A1 - Werfel, Thomas A1 - Wilsman‐Theis, Dagmar A1 - Worm, Margitta T1 - COVID‐19 and implications for dermatological and allergological diseases JF - JDDG: Journal der Deutschen Dermatologischen Gesellschaft N2 - COVID‐19, caused by the coronavirus SARS‐CoV‐2, has become pandemic. A further level of complexity opens up as soon as we look at diseases whose pathogenesis and therapy involve different immunological signaling pathways, which are potentially affected by COVID‐19. Medical treatments must often be reassessed and questioned in connection with this infection. This article summarizes the current knowledge of COVID‐19 in the light of major dermatological and allergological diseases. It identifies medical areas lacking sufficient data and draws conclusions for the management of our patients during the pandemic. We focus on common chronic inflammatory skin diseases with complex immunological pathogenesis: psoriasis, eczema including atopic dermatitis, type I allergies, autoimmune blistering and inflammatory connective tissue diseases, vasculitis, and skin cancers. Since several other inflammatory skin diseases display related or comparable immunological reactions, clustering of the various inflammatory dermatoses into different disease patterns may help with therapeutic decisions. Thus, following these patterns of skin inflammation, our review may supply treatment recommendations and thoughtful considerations for disease management even beyond the most frequent diseases discussed here. KW - COVID-19 KW - dermatology KW - allergies Y1 - 2020 U6 - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-217860 VL - 18 IS - 8 SP - 815 EP - 824 ER -