Matsuoka Naoki, Kozuru Hideko, Koga Tomohiro, Abiru Seigo, Yamasaki Kazumi, Komori Atsumasa, Fujita Yuya, Tenmoku Junpei, Asano Tomoyuki, Sato Shuzo, Suzuki Eiji, Furuya Makiko, Kobayashi Hiroko, Watanabe Hiroshi, Naganuma Atsushi, Yoshizawa Kaname, Shimada Masaaki, Ario Keisuke, Yamashita Haruhiro, Kohno Hiroshi, Kaneyoshi Toshihiko, Nakamura Minoru, Furukawa Hiroshi, Takahashi Atsushi, Kawakami Atsushi, Ohira Hiromasa, Yatsuhashi Hiroshi, Migita Kiyoshi
Clinical Research Center, Nagasaki Medical Center, Nagasaki.
Department of Rheumatology, Fukushima Medical University, Fukushima.
Medicine (Baltimore). 2019 Aug;98(35):e16924. doi: 10.1097/MD.0000000000016924.
Autoimmune hepatitis (AIH) is a disorder of unknown etiology in which immune-mediated liver damage progresses to cirrhosis or hepatocellular carcinoma (HCC). The mainstay therapy for AIH is steroids and other immunosuppressive treatments. Currently, there are no validated markers for monitoring immune-mediated hepatic inflammation. Galectin-9 has recently been identified as a potential biomarker in patients with chronic liver disease. The objective of this study was to determine whether Galectin-9 and other serum proteins are associated with active disease in AIH patients.We enrolled 77 Japanese patients with well-documented AIH who were identified from the National Hospital Organization-AIH-liver-network database, as well as 32 patients with chronic hepatitis C (CHC), 27 patients with SLE, and 17 healthy control subjects. Serum levels of galectin-9, and markers of liver injury were measured and compared between groups.Serum levels of galectin-9 were significantly higher in AIH patients than in CHC patients (13.8 ± 4.9 ng/mL vs 8.9 ± 3.0 ng/mL, P < .001) or healthy controls (13.8 ± 4.9 ng/mL vs 5.0 ± 1.3 ng/mL, P < .001). In AIH group, serum galectin-9 levels weakly correlated with alanine aminotransferase levels or total bilirubin (TB) and strongly correlated with C-X-C motif chemokine 10 (CXCL10) and Mac-2 binding protein glycosylation isomer (M2BPGi) levels, but did not correlate with the histological grade of liver fibrosis. Steroid treatment of AIH patients significantly reduced serum galectin-9 levels (14.1 ± 4.9 ng/mL vs 8.3 ± 3.8 ng/mL, P < .001). SLE patients exhibited higher galectin-9 levels, whereas the galectin-9 levels did not correlate with liver function tests such as alanine aminotransferase levels.Serum galectin-9 correlated with disease status in AIH patients and could thus be useful biomarkers to detect hepatic autoimmunity. Because circulating galectin-9 reflects autoimmune-mediated inflammation, it may have additional utility as a biomarker for other autoimmune disorders.
自身免疫性肝炎（AIH）是一种病因不明的疾病，其中免疫介导的肝损伤会进展为肝硬化或肝细胞癌（HCC）。AIH的主要治疗方法是使用类固醇和其他免疫抑制治疗。目前，尚无用于监测免疫介导的肝脏炎症的有效标志物。最近，半乳糖凝集素-9被确定为慢性肝病患者的潜在生物标志物。本研究的目的是确定半乳糖凝集素-9和其他血清蛋白是否与AIH患者的活动性疾病相关。我们纳入了77名来自国立医院组织-AIH-肝脏网络数据库的有充分记录的日本AIH患者，以及32名慢性丙型肝炎（CHC）患者、27名系统性红斑狼疮（SLE）患者和17名健康对照者。测量并比较了各组之间的半乳糖凝集素-9血清水平和肝损伤标志物。AIH患者的半乳糖凝集素-9血清水平显著高于CHC患者（13.8±4.9 ng/mL对8.9±3.0 ng/mL，P<.001）或健康对照者（13.8±4.9 ng/mL对5.0±1.3 ng/mL，P<.001）。在AIH组中，血清半乳糖凝集素-9水平与丙氨酸转氨酶水平或总胆红素（TB）呈弱相关，与C-X-C基序趋化因子10（CXCL10）和Mac-2结合蛋白糖基化异构体（M2BPGi）水平呈强相关，但与肝纤维化的组织学分级无关。AIH患者接受类固醇治疗后，血清半乳糖凝集素-9水平显著降低（14.1±4.9 ng/mL对8.3±3.8 ng/mL，P<.001）。SLE患者的半乳糖凝集素-9水平较高，而半乳糖凝集素-9水平与丙氨酸转氨酶水平等肝功能检查无关。血清半乳糖凝集素-9与AIH患者的疾病状态相关，因此可能是检测肝脏自身免疫的有用生物标志物。由于循环中的半乳糖凝集素-9反映了自身免疫介导的炎症，它可能作为其他自身免疫性疾病的生物标志物具有额外的用途。
