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Role of the intracellular receptor domain of gp130 (exon 17) in human inflammatory bowel disease

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World Journal of Gastroenterology 2005年第8期11卷 1196-1199页

作者： Christoph J.Auernhammer Kathrin Zitzmann Fabian Schnitzler Julia Seiderer peter lohse George Vlotides Dieter Engelhardt Michael Sackmann Burkhard G(o|¨)ke Thomas Ochsenkühn Department of Internal Medicine Ⅱ-Grosshadern Department of Clinical Chemistry-Grosshadern

AIM: To study the role of the intracellular receptor domain of gp130 in human inflammatory bowel disease (IBD).METHODS: We amplified and sequenced the complete exon 17 of the human gp130 gene in 146 patients with IBD. According to clinical and histopathological signs,the 146 patients with IBD were classified as having Crohn's disease (n = 73) or ulcerative colitis (n = 63),or as indeterminate status (n = 10).RESULTS: No mutations in exon 17 of the gp130 gene could be detected in any of the 146 patients with IBD ***: There is no evidence that mutations in exon 17 of the gp130 gene are involved in the pathogenesis of human IBD.

关键词： Exon 17 Inflammatory bowel disease gp130 gene

Characterization of human gene encoding SLA/LP autoantigen and its conserved homologs in mouse,fish,fly,and worm

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World Journal of Gastroenterology 2006年第6期12卷 902-907页

作者： Chun-Xia Wang Andreas Teufel Uta Cheruti Joachim Groetzinger peter R Galle Ansgar W lohse Johannes Herkel I. Department of Medicine University Medical Centre Hamburg-Eppendorf Hamburg Germany Shandong University Shandong Provincial Hospital Jinan Shandong Province China I. Department ofMedicine Johannes Gutenberg University Mainz Germany Institute of Biochemistry Christian-Albretchts-University Kiel Germany

AIM： To approach the elusive function of the SLA/LP molecule, we have characterized genomic organization and conservation of the major antigenic and functional properties of the SLA/LP molecule in various species. METHODS： By means of computational biology, we have characterized the complete SLA/LP gene, mRNA and deduced protein sequences in man, mouse, zebrafish, fly, and worm. RESULTS： The human SLA/LP gene sequence of approximately 39 kb, which maps to chromosome 4p15.2, is organized in 11 exons, of which 10 or 11 are translated, depending on the splice variant. Homologous molecules were identified in several biological model organisms. The various homologous protein sequences showed a high degree of similarity or homology, notably at those residues that are of functional importance. The only domain of the human protein sequence that lacks significant homology with homologous sequences is the major antigenic epitope recognized by autoantibodies from autoimmune hepatitis （AIH） patients. CONCLUSION： The SLA/LP molecule and its functionally relevant residues have been highly conserved throughout the evoluti n, suggesting an indispensable function of the molecule. The finding that the only non-conserved domain is the dominant antigenic epitope of the human SLA/LP sequence, suggests that SLA/LP autoimmunity is autoantigen-driven rather than being driven by molecular mimicry.

关键词： Autoimmune hepatitis Autoantigen Genomics Bioinformatics

Hepatocellular carcinoma in patients with autoimmune hepatitis

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World Journal of Gastroenterology 2009年第5期15卷 578-582页

作者： Andreas Teufel Arndt Weinmann Catherine Centner Anja Piendl Ansgar W lohse peter R Galle Stephan Kanzler Department of Medicine I Johannes Gutenberg University Mainz 55101 Germany Department of Medicine I University of Hamburg Hamburg 22527 Germany

AIM: To evaluate and confirm the low incidence of hepatocellular carcinoma (HCC) in patients with autoimmune hepatitis (AIH). At present only very few cases of HCC in patients with AIH and definite exclusion of chronic viral hepatitis have been published, suggesting that HCC due to AIH is rare. METHODS: In order to further investigate the incidence of HCC in patients with AIH, we reviewed our large cohort of 278 patients with AIH. RESULTS: Eighty-nine patients (32%) were diagnosed with liver cirrhosis, a preneoplastic condition for HCC. We studied a total of 431 patient years of cirrhosis in these patients, an average 4.8 years per patient. During this period none of the patients of our own study cohort developed HCC. However, three patients with HCC due to AIH associated liver cirrhosis were referred to our department for further treatment of HCC. In all three patients chronic viral hepatitis was excluded. CONCLUSION: We conclude that HCC may under rare circumstances develop due to chronic AIH dependent liver cirrhosis. Compared to other causes of liver cirrhosis such as chronic viral hepatitis, alcohol, or hemochromatosis, the incidence of HCC is significantly lower. Pathophysiological differences between AIH and chronic viral hepatitis responsible for differences in the incidence of HCC are yet to be further characterized and may lead to new therapeutic concepts in prevention and treatment of liver cancer.

关键词： Autoimmune hepatitis Hepatocellularcarcinoma Hepatic C virus Hepatic B virus Livercirrhosis

Genetic association of autoimmune hepatitis and human leucocyte antigen in German patients

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World Journal of Gastroenterology 2006年第34期12卷 5513-5516页

作者： Andreas Teufel Markus Wrns Arndt Weinmann Catherine Centner Anja Piendl Ansgar W lohse peter R Galle Stephan Kanzler Department of Medicine I Johannes Gutenberg University Mainz Germany Department of Medicine I University of Hamburg Germany

AIM: To report on our large German collective and updated data of 142 patients with autoimmune hepatitis (AIH) type 1. METHODS: Key investigations performed were liver biopsy, serum autoantibodies as well as serum markers such as IgG and elevated transaminases. Antinuclear antigen (ANA) and smooth muscle antigen (SMA) autoantibodies characterized type 1 AIH. Type 3 (AIH) was solely characterized by the occurrence of soluble liver antigen/liver-pancreas antigen (SLA/LP) autoantibodies either with or without ANA or SMA autoantibodies. RESULTS: Most prevalent HLAs were A2 (68 patients, 48%), B8 (63 patients, 44%), C7 (90 patients, 63%), DR3 (49 patients, 38%), DR4 (49 patients, 38%) and DQ2 (42 patients, 30%). Compared to the Italian and North American patients, we found fewer patients with a DQ2 subtype. Furthermore, the B8-DR3-DQ2 human leucocyte antigen (HLA) was also less prominent compared to the North American patients. However, prevalences of B8, DR3, DR4, DR7, DR11 and DR13 were comparable to the Italian and North American patients. Furthermore, we report on an additional subgroup of patients with SLA/LP positive AIH. Generally, in this subgroup of patients the same HLA subtypes were favoured as the AIH type 1. CONCLUSION: Although HLA subtypes were comparable between these three collectives, the German patients were distinct from the Italian and North American patients with respect to DQ2 and from the North American patients with respect to B8-DR3-DQ2HLA. A clinical correlation, e.g. difference in severity or treatability of AIH type 1, has yet to be determined.

关键词： Autoimmune hepatitis Human leucocyte antigen Immunogenetics

MORTl/FADD is involved in liver regeneration

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World Journal of Gastroenterology 2005年第46期11卷 7248-7253页

作者： Marcus Schuchmann Felix Rückert Jose F Garcia-Lazaro Andrea Karg Jürgen Burg Natalia Knorr Jürgen Siebler Eugene E Varfolomeev David Wallach Wolfgang Schreiber Ansgar W lohse peter R Galle Department of Medicine University of Mainz Langenbeckstr.1Mainz 55101 Germany Institute of RadiologyUniversity of Mainz Langenbeckstr.1Mainz 55101Germany Institute of PathologyUniversity of Mainz Langenbeckstr. 1 Mainz 55101 Germany Department of MedicineUniversity of Mainz Langenbeckstr.1Mainz 55101Germany GenentechSouth San Francisco CAUnited States The Weizmann Institute of ScienceRehovot Israel Institute of RadiologyUniversity of Mainz Langenbeckstr.1Mainz 55101 Germany Department of Medicine University of Mainz Langenbeckstr.1Mainz 55101 Germany

AIM: To explore the role of the adaptor molecule in liver regeneration after partial hepatectomy (PH). METHODS: We used transgenic mice expressing an N-terminal truncated form of MORT1/FADD under the control of the albumin promoter. As previously shown, this transgenic protein abrogated CD95- and CD120a-mediated apoptosis in the liver. Cyclin A expression was detected using Western blotting. ELISA and RT-PCR were used to detect IL-6 and IL-6 mRNA, respectively. DNA synthesis in liver tissue was measured by BrdU staining. RESULTS: Resection of 70% of the liver was followed by a reduced early regenerative response in the transgenic group at 36 h. Accordingly, 36 h after hepatectomy, cyclin A expression was only detectable in wild-type animals. Consequently, the onset of liver mass restoration was retarded as measured by MRI volumetry and mortality was significantly higher in the transgenic group. CONCLUSION: Our data demonstrate for the first time an involvement of the death receptor molecule MORT1/ FADD in liver regeneration, beyond its well described role as part of the intracellular death signaling pathway.

关键词： MORT1/FADD CD95 TNF Apoptosis Liver regeneration