Cholangiopathy and tumors of the pancreas, liver, and biliary tree in boys with X-linked immunodeficiency with hyper-IgM.
Cholangiopathy and tumors of the pancreas, liver, and biliary tree in boys with X-linked immunodeficiency with hyper-IgM.
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DOI：
10.4049/jimmunol.158.2.977
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发表时间：
1997-01
影响因子：
4.4
通讯作者：
A. Hayward;J. Levy;F. Facchetti;L. Notarangelo;H. Ochs;Amos Etzioni;J. Bonnefoy;M. Cosyns;A. Weinberg
中科院分区：
文献类型：
--
作者：
A. Hayward;J. Levy;F. Facchetti;L. Notarangelo;H. Ochs;Amos Etzioni;J. Bonnefoy;M. Cosyns;A. Weinberg
我们报告了 X 连锁免疫缺陷伴高 IgM (XHIM) 与影响肝脏、胰腺、胆管树和相关神经外胚层内分泌细胞的癌症之间的关联。九个病例中有八个肿瘤是致命的，并且在大多数情况下，先有慢性胆管病和/或肝硬化。另外一组患有 XHIM 的受试者患有肝脏或胆管慢性炎症，但没有恶性肿瘤。许多 XHIM 患者感染了隐孢子虫。 CD40 通常在再生或发炎的胆管上皮上表达。当细胞表面 CD40 通过 CD40 配体融合蛋白交联时，对隐孢子虫和 CMV 感染敏感的 CD40+ 肝细胞癌细胞系 HepG2 变得耐药。如果放线菌酮阻断蛋白质合成或细胞被隐孢子虫感染，HepG2 细胞就会触发细胞凋亡。 CD40 在胆管上皮上的连接可能有助于防御细胞内病原体的感染。我们认为，导致 XHIM 的 CD40 配体突变剥夺了胆管上皮针对细胞内病原体的一层防线，并且胆管树的恶性转化发生在慢性感染或炎症之后。由此产生的肿瘤可能会在没有有效免疫反应检查的情况下进展。肝功能检查异常的 XHIM 患者应被视为胆管病或恶性肿瘤的风险增加。
We report an association between X-linked immunodeficiency with hyper-IgM (XHIM) and carcinomas affecting the liver, pancreas, biliary tree, and associated neuroectodermal endocrine cells. The tumors were fatal in eight of nine cases and in most instances were preceded by chronic cholangiopathy and/or cirrhosis. An additional group of subjects with XHIM had chronic inflammation of the liver or bile ducts but no malignancy. Many patients with XHIM were infected with cryptosporidia. CD40 is normally expressed on regenerating or inflammed bile duct epithelium. A CD40+ hepatocellular carcinoma cell line, HepG2, susceptible to cryptosporidia and CMV infection became resistant when cell surface CD40 was cross-linked by a CD40 ligand fusion protein. Apoptosis was triggered in HepG2 cells if protein synthesis was blocked by cycloheximide or if the cells were infected by cryptosporidia. Ligation of CD40 on biliary epithelium may contribute to defense against infection by intracellular pathogens. We propose that the CD40 ligand mutations that cause XHIM deprive the biliary epithelium of one line of defense against intracellular pathogens and that malignant transformation in the biliary tree follows chronic infection or inflammation. The resulting tumors may then progress without check by an effective immune response. Patients with XHIM who have abnormal liver function tests should be considered at increased risk for cholangiopathy or malignancy.