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Int J Med Sci 2014; 11(9):850-856. doi:10.7150/ijms.8633

Research Paper

Presence of Antibodies against Self Human Leukocyte Antigen Class II Molecules in Autoimmune Hepatitis

Satoshi Yamagiwa1✉, Hiroteru Kamimura1, Masaaki Takamura1, Takuya Genda2, Takafumi Ichida2*, Minoru Nomoto1, Yutaka Aoyagi1

1. Division of Gastroenterology and Hepatology, Niigata University Graduate School of Medical and Dental Sciences, 1-757 Asahimachi-dori, Chuo-ku, Niigata 951-8510, Japan;
2. Department of Gastroenterology and Hepatology, Juntendo University Shizuoka Hospital, 1129 Nagaoka, Izunokuni 410-2295, Japan.
* Present address: Department of Gastroenterology and Hepatology, Shonan Tobe General Hospital, 500 Nishikubo, Chigasaki 253-0083, Japan.


Autoimmune hepatitis (AIH) can arise de novo after liver transplantation (LT) for non-autoimmune liver diseases. Considering the identical features of de novo AIH after LT and classical AIH, as well as the importance of anti-human leukocyte antigen (HLA) antibodies in graft rejection, we investigated the presence of circulating anti-HLA class II antibodies in the sera of 35 patients with AIH, 30 patients with primary biliary cirrhosis (PBC), and 30 healthy donors using fluorescent dye-impregnated beads bound to HLA molecules. We then investigated the allele specificity of the antibodies and identified the HLA alleles in each patient using DNA-based HLA typing. We also examined HLA class II expression in liver samples using immunohistochemistry. Anti-HLA class II antibodies were detected significantly more frequently in the patients with AIH (88.1%) than in the patients with PBC (33.3%) or in the healthy donors (13.3%) (both P <0.01). We confirmed that the anti-HLA class II antibodies in the AIH patients showed specificity for several HLA class II alleles, including self HLA class II alleles. Moreover, positive reactivity with anti-self HLA class II antibodies was associated with higher serum transaminase levels. In conclusion, we demonstrated, for the first time, that antibodies against self HLA class II alleles were detectable in patients with AIH. Our results suggest that an antibody-mediated immune response against HLA class II molecules on hepatocytes may be involved in the pathogenesis or acceleration of liver injury in AIH.

Keywords: HLA, AIH, PBC, anti-HLA antibodies.

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How to cite this article:
Yamagiwa S, Kamimura H, Takamura M, Genda T, Ichida T, Nomoto M, Aoyagi Y. Presence of Antibodies against Self Human Leukocyte Antigen Class II Molecules in Autoimmune Hepatitis. Int J Med Sci 2014; 11(9):850-856. doi:10.7150/ijms.8633. Available from