BACKGROUND Abatacept is increasingly used for rheumatoid arthritis (RA) and juvenile idiophathic arthritis (JIA) treatment. However little is known about the risk of hepatotoxicity. The aim of this study was to determine whether the inhibition of the T cell CD28 receptor by abatacept results in acute hepatitis in BALB/c mice. METHODS Twenty BALB/c mice were studied. Ten mice received subcutaneous (SC) injection of abatacept (0.25mg per 25g body weight per 0.03 ml normal saline) at 0, 2, 4 and 8 weeks. For the control group, 10 mice received a SC injection of normal saline (NS) (0.03 ml). At the 10th week post injection, the mice were sacrificed, and histopathological studies were conducted. RESULTS Of the abatacept-treated group, 3/10 mice died. Liver histology for the abatacept-treated group showed that 6/7 displayed histopathological changes in the lobular cellular infiltrates of eosinophils, lymphocytes and histiocytes, in addition to granuloma formation. In contrast, only minimal inflammation was observed in 3/10 mice in the control group (p=0.036). CONCLUSION Abatacept may play a role in inducing granulomatous hepatitis with a sarcoidosis-like reaction. Additional data including transaminases, antinuclear antibodies (ANA), Antimitochondrial antibodies (AMA) and other auto antibodies should be tested.

中文翻译：

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阿巴西普诱发肉芽肿性肝炎并伴有结节病样反应：小鼠双盲试验。

背景阿巴西普越来越多地用于类风湿性关节炎(RA)和幼年特发性关节炎(JIA)的治疗。然而，人们对肝毒性的风险知之甚少。本研究的目的是确定阿巴西普对 T 细胞 CD28 受体的抑制是否会导致 BALB/c 小鼠发生急性肝炎。方法 对 20 只 BALB/c 小鼠进行了研究。10只小鼠在第0、2、4和8周时接受皮下（SC）注射阿巴西普（每25克体重0.25毫克/0.03毫升生理盐水）。对于对照组，10只小鼠接受皮下注射生理盐水(NS)(0.03ml)。注射后第10周，处死小鼠，并进行组织病理学研究。结果 在阿巴西普治疗组中，3/10 的小鼠死亡。阿巴西普治疗组的肝脏组织学显示，除肉芽肿形成外，6/7 的小叶细胞浸润有嗜酸性粒细胞、淋巴细胞和组织细胞，显示出组织病理学变化。相比之下，对照组中 3/10 的小鼠仅观察到轻微的炎症 (p=0.036)。结论 阿巴西普可能在诱发肉芽肿性肝炎伴结节病样反应中发挥作用。应测试其他数据，包括转氨酶、抗核抗体 (ANA)、抗线粒体抗体 (AMA) 和其他自身抗体。