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Year of publication
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- English (12)
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- yes (12)
Is part of the Bibliography
- no (12) (remove)
Keywords
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- CD137 (1)
- CVID (1)
- EGFR (1)
- European Society for Immunodeficiencies (ESID) (1)
- German PID-NET registry (1)
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- PID prevalence (1)
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Institute
- Medizin (12) (remove)
Forstner, Andreas Josef ; Hecker, Julian ; Hofmann, Andrea ; Maaser, Anna ; Reinbold, Céline S. ; Mühleisen, Thomas W. ; Leber, Markus ; Strohmaier, Jana ; Degenhardt, Franziska ; Treutlein, Jens ; Mattheisen, Manuel ; Schumacher, Johannes ; Streit, Fabian ; Meier, Sandra ; Herms, Stefan ; Hoffmann, Per ; Lacour, André ; Witt, Stephanie ; Reif, Andreas ; Müller-Myhsok, Bertram ; Lucae, Susanne ; Maier, Wolfgang ; Schwarz, Markus ; Vedder, Helmut ; Kammerer-Ciernioch, Jutta ; Pfennig, Andrea ; Bauer, Michael ; Hautzinger, Martin ; Moebus, Susanne ; Schenk, Lorena M. ; Fischer, Sascha B. ; Sivalingam, Sugirthan ; Czerski, Piotr M. ; Hauser, Joanna ; Lissowska, Jolanta ; Szeszenia-Dabrowska, Neonila ; Brennan, Paul E. ; McKay, James D. ; Wright, Adam ; Mitchell, Philip B. ; Fullerton, Janice M. ; Schofield, Peter R. ; Montgomery, Grant W. ; Medland, Sarah E. ; Gordon, Scott D. ; Martin, Nicholas Gordon ; Krasnov, Valery ; Chuchalin, Alexander ; Babadjanova, Gulja ; Pantelejeva, Galina ; Abramova, Lilia I. ; Tiganov, Alexander S. ; Polonikov, Alexey ; Khusnutdinova, Elza ; Alda, Martin ; Cruceanu, Cristiana ; Rouleau, Guy A. ; Turecki, Gustavo ; Laprise, Catherine ; Rivas, Fabio ; Mayoral, Fermı́n ; Kogevinas, Manolis ; Grigoroiu-Serbanescu, Maria ; Becker, Tim ; Schulze, Thomas Gerd ; Rietschel, Marcella ; Cichon, Sven ; Fier, Heide ; Nöthen, Markus Maria
Bipolar disorder (BD) is a highly heritable neuropsychiatric disease characterized by recurrent episodes of mania and depression. BD shows substantial clinical and genetic overlap with other psychiatric disorders, in particular schizophrenia (SCZ). The genes underlying this etiological overlap remain largely unknown. A recent SCZ genome wide association study (GWAS) by the Psychiatric Genomics Consortium identified 128 independent genome-wide significant single nucleotide polymorphisms (SNPs). The present study investigated whether these SCZ-associated SNPs also contribute to BD development through the performance of association testing in a large BD GWAS dataset (9747 patients, 14278 controls). After re-imputation and correction for sample overlap, 22 of 107 investigated SCZ SNPs showed nominal association with BD. The number of shared SCZ-BD SNPs was significantly higher than expected (p = 1.46x10-8). This provides further evidence that SCZ-associated loci contribute to the development of BD. Two SNPs remained significant after Bonferroni correction. The most strongly associated SNP was located near TRANK1, which is a reported genome-wide significant risk gene for BD. Pathway analyses for all shared SCZ-BD SNPs revealed 25 nominally enriched gene-sets, which showed partial overlap in terms of the underlying genes. The enriched gene-sets included calcium- and glutamate signaling, neuropathic pain signaling in dorsal horn neurons, and calmodulin binding. The present data provide further insights into shared risk loci and disease-associated pathways for BD and SCZ. This may suggest new research directions for the treatment and prevention of these two major psychiatric disorders.
Harter, Patrick Nikolaus ; Blank, Anna-Eva ; Weide, Benjamin ; Beschorner, Rudi ; Bernatz, Simon ; Baumgarten, Peter ; Braczynski, Anne Kristin ; Hattingen, Elke ; Ronellenfitsch, Michael Wilfried ; Schwarz, Herbert ; Mittelbronn, Michel Guy André
Aim: The cytokine receptor tumor necrosis factor receptor superfamily member 9 (TNFRSF9) is mainly considered to be a co-stimulatory activation marker in hematopoietic cells. Several preclinical models have shown a dramatic beneficial effect of treatment approaches targeting TNFRSF9 with agonistic antibodies. However, preliminary clinical phase I/II studies were stopped after the occurrence of several severe deleterious side effects. In a previous study, it was demonstrated that TNFRSF9 was strongly expressed by reactive astrocytes in primary central nervous system (CNS) tumors, but was largely absent from tumor or inflammatory cells. The aim of the present study was to address the cellular source of TNFRSF9 expression in the setting of human melanoma brain metastasis, a highly immunogenic tumor with a prominent tropism to the CNS.
Methods: Melanoma brain metastasis was analyzed in a cohort of 78 patients by immunohistochemistry for TNFRSF9 and its expression was correlated with clinicopathological parameters including sex, age, survival, tumor size, number of tumor spots, and BRAF V600E expression status.
Results: Tumor necrosis factor receptor superfamily member 9 was frequently expressed independently on both melanoma and endothelial cells. In addition, TNFRSF9 was also present on smooth muscle cells of larger vessels and on a subset of lymphomonocytic tumor infiltrates. No association between TNFRSF9 expression and patient survival or other clinicopathological parameters was seen. Of note, several cases showed a gradual increase in TNFRSF9 expression on tumor cells with increasing distance from blood vessels, an observation that might be linked to hypoxia-driven TNFRSF9 expression in tumor cells.
Conclusion: The findings indicate that the cellular source of TNFRSF9 in melanoma brain metastasis largely exceeds the lymphomonocytic pool, and therefore further careful (re-) assessment of potential TNFRSF9 functions in cell types other than hematopoietic cells is needed. Furthermore, the hypothesis of hypoxia-driven TNFRSF9 expression in brain metastasis melanoma cells requires further functional testing.