原发性硬化性胆管炎(PSC)是一种慢性进行性肝病。已经描述了PSC的子类型,最近PSC血清和/或组织IgG4亚类升高。我们的目的是总结临床表型,疾病关联,鉴别诊断,对PSC高IgG4亚型的治疗反应和致病机制。我们回顾了PubMed,MEDLINE和Embase的搜索术语“原发性硬化性胆管炎”,\"IgG4\",和“IgG4相关性硬化性胆管炎(IgG4-SC)”。高达四分之一的血清IgG4被发现,在多达五分之一的PSC患者中,肝脏和胆管中发现了丰富的IgG4浆细胞浸润。该组具有独特的临床表型,一些研究报告肝脏和相关的炎症性肠病更具侵略性,与PSC-正常IgG4和疾病模拟IgG4-SC相比。区分PSC高IgG4和IgG4-SC仍然具有挑战性,需要仔细评估临床特征,器官受累和组织形态学。已经报道了血清IgG4:IgG1比率的计算和新的IgG4:IgGRNA比率的使用具有区分IgG4-SC和PSC高IgG4的优异特异性,但需要在更大的群组中进行验证。糖皮质激素治疗在PSC高IgG4中的作用仍未得到解决,担心毒性增加和缺乏结果数据。PSC中突出的IgG4抗体基础的免疫驱动因子未完全定义。与PSC高IgG4和HLAII类单倍型(B*07,DRB1*15)相关,已经描述了T-helper2和T-调节细胞因子(IL4、IL10、IL13)和趋化因子(CCL1、CCR8)。PSC高IgG4具有独特的临床表型,需要与IgG4-SC仔细区分,尽管对免疫抑制治疗的反应和长期结局仍未解决。IgG4的存在可能代表遗传易感个体中持续抗原暴露的慢性激活。
Primary sclerosing cholangitis (PSC) is a chronic progressive liver disease. Sub-types of PSC have been described, most recently PSC with elevated serum and/or tissue IgG4 subclass. We aim to summarise the clinical phenotype, disease associations, differential diagnosis, response to therapy and pathogenic mechanisms underlying PSC-high IgG4 subtype. We reviewed PubMed, MEDLINE and Embase with the search terms \"primary sclerosing cholangitis\", \"IgG4\", and \"IgG4-related sclerosing cholangitis (IgG4-SC)\". Elevated serum IgG4 are found in up-to one-quarter, and abundant IgG4-plasma cell infiltrates in the liver and bile ducts are found in up-to one-fifth of PSC patients. This group have a distinct clinical phenotype, with some studies reporting a more aggressive course of liver and associated inflammatory bowel disease, compared to PSC-normal IgG4 and the disease mimic IgG4-SC. Distinguishing PSC-high IgG4 from IgG4-SC remains challenging, requiring careful assessment of clinical features, organ involvement and tissue morphology. Calculation of serum IgG4:IgG1 ratios and use of a novel IgG4:IgG RNA ratio have been reported to have excellent specificity to distinguish IgG4-SC and PSC-high IgG4 but require validation in larger cohorts. A role for corticosteroid therapy in PSC-high IgG4 remains unanswered, with concerns of increased toxicity and lack of outcome data. The immunological drivers underlying prominent IgG4 antibodies in PSC are incompletely defined. An association with PSC-high IgG4 and HLA class-II haplotypes (B*07, DRB1*15), T-helper2 and T-regulatory cytokines (IL4, IL10, IL13) and chemokines (CCL1, CCR8) have been described. PSC-high IgG4 have a distinct clinical phenotype and need careful discrimination from IgG4-SC, although response to immunosuppressive treatments and long-term outcome remains unresolved. The presence of IgG4 likely represents chronic activation to persistent antigenic exposure in genetically predisposed individuals.