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  - Koch, Elias A. T.
A1  - Petzold, Anne
A1  - Wessely, Anja
A1  - Dippel, Edgar
A1  - Gesierich, Anja
A1  - Gutzmer, Ralf
A1  - Hassel, Jessica C.
A1  - Haferkamp, Sebastian
A1  - Kähler, Katharina C.
A1  - Knorr, Harald
A1  - Kreuzberg, Nicole
A1  - Leiter, Ulrike
A1  - Loquai, Carmen
A1  - Meier, Friedegund
A1  - Meissner, Markus
A1  - Mohr, Peter
A1  - Pföhler, Claudia
A1  - Rahimi, Farnaz
A1  - Schadendorf, Dirk
A1  - Schell, Beatrice
A1  - Schlaak, Max
A1  - Terheyden, Patrick
A1  - Thoms, Kai-Martin
A1  - Schuler-Thurner, Beatrice
A1  - Ugurel, Selma
A1  - Ulrich, Jens
A1  - Utikal, Jochen
A1  - Weichenthal, Michael
A1  - Ziller, Fabian
A1  - Berking, Carola
A1  - Heppt, Markus V.
T1  - Immune checkpoint blockade for metastatic uveal melanoma: re-induction following resistance or toxicity
JF  - Cancers
N2  - Re-induction with immune checkpoint blockade (ICB) needs to be considered in many patients with uveal melanoma (UM) due to limited systemic treatment options. Here, we provide hitherto the first analysis of ICB re-induction in UM. A total of 177 patients with metastatic UM treated with ICB were included from German skin cancer centers and the German national skin cancer registry (ADOReg). To investigate the impact of ICB re-induction, two cohorts were compared: patients who received at least one ICB re-induction (cohort A, n = 52) versus those who received only one treatment line of ICB (cohort B, n = 125). In cohort A, a transient benefit of overall survival (OS) was observed at 6 and 12 months after the treatment start of ICB. There was no significant difference in OS between both groups (p = 0.1) with a median OS of 16.2 months (cohort A, 95% CI: 11.1–23.8) versus 9.4 months (cohort B, 95% CI: 6.1–14.9). Patients receiving re-induction of ICB (cohort A) had similar response rates compared to those receiving ICB once. Re-induction of ICB may yield a clinical benefit for a small subgroup of patients even after resistance or development of toxicities.
KW  - uveal melanoma
KW  - immune checkpoint blockade
KW  - PD-1
KW  - CTLA-4
KW  - re-induction
KW  - treatment resistance
KW  - toxicity
Y1  - 2022
U6  - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-254814
SN  - 2072-6694
VL  - 14
IS  - 3
ER  - 
TY  - JOUR
A1  - Koch, Elias A. T.
A1  - Petzold, Anne
A1  - Wessely, Anja
A1  - Dippel, Edgar
A1  - Gesierich, Anja
A1  - Gutzmer, Ralf
A1  - Hassel, Jessica C.
A1  - Haferkamp, Sebastian
A1  - Hohberger, Bettina
A1  - Kähler, Katharina C.
A1  - Knorr, Harald
A1  - Kreuzberg, Nicole
A1  - Leiter, Ulrike
A1  - Loquai, Carmen
A1  - Meier, Friedegund
A1  - Meissner, Markus
A1  - Mohr, Peter
A1  - Pföhler, Claudia
A1  - Rahimi, Farnaz
A1  - Schadendorf, Dirk
A1  - Schell, Beatrice
A1  - Schlaak, Max
A1  - Terheyden, Patrick
A1  - Thoms, Kai-Martin
A1  - Schuler-Thurner, Beatrice
A1  - Ugurel, Selma
A1  - Ulrich, Jens
A1  - Utikal, Jochen
A1  - Weichenthal, Michael
A1  - Ziller, Fabian
A1  - Berking, Carola
A1  - Heppt, Markus
T1  - Immune checkpoint blockade for metastatic uveal melanoma: patterns of response and survival according to the presence of hepatic and extrahepatic metastasis
JF  - Cancers
N2  - Background: Since there is no standardized and effective treatment for advanced uveal melanoma (UM), the prognosis is dismal once metastases develop. Due to the availability of immune checkpoint blockade (ICB) in the real-world setting, the prognosis of metastatic UM has improved. However, it is unclear how the presence of hepatic and extrahepatic metastasis impacts the response and survival after ICB. Methods: A total of 178 patients with metastatic UM treated with ICB were included in this analysis. Patients were recruited from German skin cancer centers and the German national skin cancer registry (ADOReg). To investigate the impact of hepatic metastasis, two cohorts were compared: patients with liver metastasis only (cohort A, n = 55) versus those with both liver and extra-hepatic metastasis (cohort B, n = 123). Data were analyzed in both cohorts for response to treatment, progression-free survival (PFS), and overall survival (OS). The survival and progression probabilities were calculated with the Kaplan–Meier method. Log-rank tests, χ\(^2\) tests, and t-tests were performed to detect significant differences between both cohorts. Results: The median OS of the overall population was 16 months (95% CI 13.4–23.7) and the median PFS, 2.8 months (95% CI 2.5–3.0). The median OS was longer in cohort B than in cohort A (18.2 vs. 6.1 months; p = 0.071). The best objective response rate to dual ICB was 13.8% and to anti-PD-1 monotherapy 8.9% in the entire population. Patients with liver metastases only had a lower response to dual ICB, yet without significance (cohort A 8.7% vs. cohort B 16.7%; p = 0.45). Adverse events (AE) occurred in 41.6%. Severe AE were observed in 26.3% and evenly distributed between both cohorts. Conclusion: The survival of this large cohort of patients with advanced UM was more favorable than reported in previous benchmark studies. Patients with both hepatic and extrahepatic metastasis showed more favorable survival and higher response to dual ICB than those with hepatic metastasis only.
KW  - uveal melanoma
KW  - immune checkpoint blockade
KW  - PD-1
KW  - CTLA-4
KW  - liver metastasis
KW  - treatment resistance
Y1  - 2021
U6  - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-242603
SN  - 2072-6694
VL  - 13
IS  - 13
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  -