Systemic and local expression levels of TNF-like ligand 1A and its decoy receptor 3 are increased in primary biliary cirrhosis
Yoshihiro Aiba
Clinical Research Center, National Hospital Organization Nagasaki Medical Center, Omura, Japan
Search for more papers by this authorKenichi Harada
Department of Human Pathology, Kanazawa University Graduate School of Medicine, Kanazawa, Japan
Search for more papers by this authorAtsumasa Komori
Clinical Research Center, National Hospital Organization Nagasaki Medical Center, Omura, Japan
Department of Hepatology, Nagasaki University Graduate School of Biomedical Sciences, Omura, Japan
Search for more papers by this authorMasahiro Ito
Clinical Research Center, National Hospital Organization Nagasaki Medical Center, Omura, Japan
Department of Hepatology, Nagasaki University Graduate School of Biomedical Sciences, Omura, Japan
Search for more papers by this authorShinji Shimoda
Medicine and Biosystemic Science, Kyushu University Graduate School of Medical Sciences, Fukuoka, Japan
Search for more papers by this authorHitomi Nakamura
Clinical Research Center, National Hospital Organization Nagasaki Medical Center, Omura, Japan
Search for more papers by this authorShinya Nagaoka
Clinical Research Center, National Hospital Organization Nagasaki Medical Center, Omura, Japan
Search for more papers by this authorSeigo Abiru
Clinical Research Center, National Hospital Organization Nagasaki Medical Center, Omura, Japan
Search for more papers by this authorKiyoshi Migita
Clinical Research Center, National Hospital Organization Nagasaki Medical Center, Omura, Japan
Department of Hepatology, Nagasaki University Graduate School of Biomedical Sciences, Omura, Japan
Search for more papers by this authorHiromi Ishibashi
International University of Health and Welfare/Fukuoka Sanno Hospital, Fukuoka, Japan
Search for more papers by this authorYasuni Nakanuma
Department of Human Pathology, Kanazawa University Graduate School of Medicine, Kanazawa, Japan
Search for more papers by this authorNao Nishida
Department of Human Genetics, Graduate School of Medicine, The University of Tokyo, Tokyo, Japan
Search for more papers by this authorMinae Kawashima
Department of Human Genetics, Graduate School of Medicine, The University of Tokyo, Tokyo, Japan
Search for more papers by this authorKatsushi Tokunaga
Department of Human Genetics, Graduate School of Medicine, The University of Tokyo, Tokyo, Japan
Search for more papers by this authorHiroshi Yatsuhashi
Clinical Research Center, National Hospital Organization Nagasaki Medical Center, Omura, Japan
Department of Hepatology, Nagasaki University Graduate School of Biomedical Sciences, Omura, Japan
Search for more papers by this authorCorresponding Author
Minoru Nakamura
Clinical Research Center, National Hospital Organization Nagasaki Medical Center, Omura, Japan
Department of Hepatology, Nagasaki University Graduate School of Biomedical Sciences, Omura, Japan
Headquarters of PBC Research in the National Hospital Organization Study Group for Liver Disease in Japan (NHOSLJ), Omura, Japan
Correspondence
Minoru Nakamura, MD, PhD, Headquarters of PBC Research in NHOSLJ, Clinical Research Center, National Hospital Organization Nagasaki Medical Center and Department of Hepatology, Nagasaki University Graduate School of Biomedical Sciences, Kubara 2-1001-1, Omura, Nagasaki 856-8562, Japan
Tel: +81 957 52 3121
Fax: +81 957 53 6675
e-mail: [email protected]
Search for more papers by this authorYoshihiro Aiba
Clinical Research Center, National Hospital Organization Nagasaki Medical Center, Omura, Japan
Search for more papers by this authorKenichi Harada
Department of Human Pathology, Kanazawa University Graduate School of Medicine, Kanazawa, Japan
Search for more papers by this authorAtsumasa Komori
Clinical Research Center, National Hospital Organization Nagasaki Medical Center, Omura, Japan
Department of Hepatology, Nagasaki University Graduate School of Biomedical Sciences, Omura, Japan
Search for more papers by this authorMasahiro Ito
Clinical Research Center, National Hospital Organization Nagasaki Medical Center, Omura, Japan
Department of Hepatology, Nagasaki University Graduate School of Biomedical Sciences, Omura, Japan
Search for more papers by this authorShinji Shimoda
Medicine and Biosystemic Science, Kyushu University Graduate School of Medical Sciences, Fukuoka, Japan
Search for more papers by this authorHitomi Nakamura
Clinical Research Center, National Hospital Organization Nagasaki Medical Center, Omura, Japan
Search for more papers by this authorShinya Nagaoka
Clinical Research Center, National Hospital Organization Nagasaki Medical Center, Omura, Japan
Search for more papers by this authorSeigo Abiru
Clinical Research Center, National Hospital Organization Nagasaki Medical Center, Omura, Japan
Search for more papers by this authorKiyoshi Migita
Clinical Research Center, National Hospital Organization Nagasaki Medical Center, Omura, Japan
Department of Hepatology, Nagasaki University Graduate School of Biomedical Sciences, Omura, Japan
Search for more papers by this authorHiromi Ishibashi
International University of Health and Welfare/Fukuoka Sanno Hospital, Fukuoka, Japan
Search for more papers by this authorYasuni Nakanuma
Department of Human Pathology, Kanazawa University Graduate School of Medicine, Kanazawa, Japan
Search for more papers by this authorNao Nishida
Department of Human Genetics, Graduate School of Medicine, The University of Tokyo, Tokyo, Japan
Search for more papers by this authorMinae Kawashima
Department of Human Genetics, Graduate School of Medicine, The University of Tokyo, Tokyo, Japan
Search for more papers by this authorKatsushi Tokunaga
Department of Human Genetics, Graduate School of Medicine, The University of Tokyo, Tokyo, Japan
Search for more papers by this authorHiroshi Yatsuhashi
Clinical Research Center, National Hospital Organization Nagasaki Medical Center, Omura, Japan
Department of Hepatology, Nagasaki University Graduate School of Biomedical Sciences, Omura, Japan
Search for more papers by this authorCorresponding Author
Minoru Nakamura
Clinical Research Center, National Hospital Organization Nagasaki Medical Center, Omura, Japan
Department of Hepatology, Nagasaki University Graduate School of Biomedical Sciences, Omura, Japan
Headquarters of PBC Research in the National Hospital Organization Study Group for Liver Disease in Japan (NHOSLJ), Omura, Japan
Correspondence
Minoru Nakamura, MD, PhD, Headquarters of PBC Research in NHOSLJ, Clinical Research Center, National Hospital Organization Nagasaki Medical Center and Department of Hepatology, Nagasaki University Graduate School of Biomedical Sciences, Kubara 2-1001-1, Omura, Nagasaki 856-8562, Japan
Tel: +81 957 52 3121
Fax: +81 957 53 6675
e-mail: [email protected]
Search for more papers by this authorAbstract
Background & Aims
Through a genome-wide association study of a Japanese population, we recently identified TNFSF15, a gene encoding TNF-like ligand 1A (TL1A), as a susceptibility gene for primary biliary cirrhosis (PBC). We investigated the clinical significance of TL1A and one of its receptors, decoy receptor 3 (DcR3), in PBC.
Methods
We analysed the systemic and local expression of TL1A and DcR3 in 110 PBC patients and 46 healthy controls using enzyme-linked immunosorbent assay, quantitative polymerase chain reaction and immunohistochemical staining.
Results
Serum TL1A levels were significantly increased in PBC patients at both early and late stages as compared with healthy controls, and its levels were significantly decreased in early-stage PBC patients after ursodeoxycholic acid (UDCA) treatment. TL1A was immunohistochemically localized to biliary epithelial cells, Kupffer cells, blood vessels and infiltrating mononuclear cells in the PBC liver. In addition, TL1A messenger RNA expression was increased in the PBC liver as compared with the non-diseased liver. Serum DcR3 levels were also significantly increased in PBC patients, and were significantly decreased after UDCA treatment in early-stage PBC patients.
Conclusions
These results indicate that TL1A and DcR3 may play an important role in the pathogenesis of PBC.
Supporting Information
| Filename | Description |
|---|---|
| liv12296-sup-0001-Figurelegends.docWord document, 24.5 KB | |
| liv12296-sup-0002-FigS1.pdfapplication/PDF, 65.4 KB | Fig. S1. Correlation between TL1A levels and biochemical parameters in sera of PBC patients. The correlations between levels of TL1A and those of ALP (A), ALT (B) or total IgM (C) in sera of PBC patients were analysed by Spearman's rank test; the correlation coefficient and P-value are shown. |
| liv12296-sup-0003-FigS2.pdfapplication/PDF, 463 KB | Fig. S2. Serum TL1A levels in antinuclear antibody-positive and -negative PBC patients. Serum TL1A levels were compared between PBC patients who were positive and negative for anti-gp210 (A) and anticentromere (B) antibodies (anti-gp210 negative vs. positive: n = 68, 5.4 ± 5.9 ng/ml vs. n = 41, 4.1 ± 3.3 ng/ml; anticentromere negative vs. positive: n = 79, 5.0 ± 5.4 ng/ml vs. n = 30, 4.4 ± 3.7 ng/ml). Statistical differences were analysed using a two-tailed Mann–Whitney U-test. |
Please note: The publisher is not responsible for the content or functionality of any supporting information supplied by the authors. Any queries (other than missing content) should be directed to the corresponding author for the article.
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