Department of Gastroenterology & Hepatology, Tytgat Institute for Liver and Intestinal Research, AGEM, Amsterdam University Medical Centers, Amsterdam, the Netherlands.
Department of Gastroenterology & Hepatology, Tytgat Institute for Liver and Intestinal Research, AGEM, Amsterdam University Medical Centers, Amsterdam, the Netherlands; Division of Hepatology, Department of Medicine II, Leipzig University Medical Center, Leipzig, Germany.
J Hepatol. 2023 Dec;79(6):1502-1523. doi: 10.1016/j.jhep.2023.08.005. Epub 2023 Aug 18.
IgG4-related cholangitis (IRC) is the major hepatobiliary manifestation of IgG4-related disease (IgG4-RD), a systemic fibroinflammatory disorder. The pathogenesis of IgG4-RD and IRC is currently viewed as multifactorial, as there is evidence of a genetic predisposition while environmental factors, such as blue-collar work, are major risk factors. Various autoantigens have been described in IgG4-RD, including annexin A11 and laminin 511-E8, proteins which may exert a partially protective function in cholangiocytes by enhancing secretion and barrier function, respectively. For the other recently described autoantigens, galectin-3 and prohibitin 1, a distinct role in cholangiocytes appears less apparent. In relation to these autoantigens, oligoclonal expansions of IgG4 plasmablasts are present in patients with IRC and disappear upon successful treatment. More recently, specific T-cell subtypes including regulatory T cells, follicular T helper 2 cells, peripheral T helper cells and cytotoxic CD8 and CD4 SLAMF7 T cells have been implicated in the pathogenesis of IgG4-RD. The clinical presentation of IRC often mimics other biliary diseases such as primary sclerosing cholangitis or cholangiocarcinoma, which may lead to inappropriate medical and potentially invalidating surgical interventions. As specific biomarkers are lacking, diagnosis is made according to the HISORt criteria comprising histopathology, imaging, serology, other organ manifestations and response to therapy. Treatment of IRC aims to prevent or alleviate organ damage and to improve symptoms and consists of (i) remission induction, (ii) remission maintenance and (iii) long-term management. Glucocorticosteroids are highly effective for remission induction, after which immunomodulators can be introduced for maintenance of remission as glucocorticosteroid-sparing alternatives. Increased insight into the pathogenesis of IRC will lead to improved diagnosis and novel therapeutic strategies in the future.
IgG4 相关性胆管炎（IRC）是 IgG4 相关疾病（IgG4-RD）的主要肝胆表现，是一种系统性纤维炎症性疾病。目前认为 IgG4-RD 和 IRC 的发病机制是多因素的，有遗传易感性的证据，而环境因素，如蓝领工作，是主要的危险因素。在 IgG4-RD 中已经描述了各种自身抗原，包括膜联蛋白 A11 和层粘连蛋白 511-E8，这些蛋白质可能通过分别增强分泌和屏障功能在胆管细胞中发挥部分保护作用。对于其他最近描述的自身抗原，半乳糖凝集素-3 和抑制素 1，在胆管细胞中的作用似乎不太明显。与这些自身抗原有关，IRC 患者存在 IgG4 浆母细胞的寡克隆扩增，在成功治疗后消失。最近，包括调节性 T 细胞、滤泡辅助 T 细胞 2、外周辅助 T 细胞和细胞毒性 CD8 和 CD4 SLAMF7 T 细胞在内的特定 T 细胞亚型被认为与 IgG4-RD 的发病机制有关。IRC 的临床表现常模仿其他肝胆疾病，如原发性硬化性胆管炎或胆管癌，这可能导致不适当的医疗和潜在无效的手术干预。由于缺乏特异性生物标志物，因此根据包含组织病理学、影像学、血清学、其他器官表现和对治疗的反应的 HISORt 标准进行诊断。IRC 的治疗旨在预防或减轻器官损伤，改善症状，包括（i）缓解诱导，（ii）缓解维持和（iii）长期管理。糖皮质激素对缓解诱导非常有效，之后可以引入免疫调节剂来维持缓解，作为糖皮质激素替代方案。对 IRC 发病机制的深入了解将导致未来改善诊断和新的治疗策略。
