Berglin Lena, Björkström Niklas K, Bergquist Annika
Liver Immunology Laboratory, Unit of Gastroenterology and Hepatology, Department of Medicine, Karolinska Institutet, Karolinska University Hospital Huddinge, Stockholm, Sweden.
Scand J Gastroenterol. 2013 Jun;48(6):719-28. doi: 10.3109/00365521.2013.786131.
Primary sclerosing cholangitis (PSC) is a chronic liver disease characterized by progressive destruction of the biliary tract system. Autoimmune reactions have been suggested to play a role in the etiology and pathogenesis of PSC, and a large number of different autoantibodies have been reported in PSC patients. However, the role of IgA, being the dominant immunoglobulin in bile and transported there via biliary epithelial cells, is still incompletely understood in PSC. The aim of this study was to evaluate the presence of autoreactive IgA in PSC patients.
Cultures of biliary epithelial cells from healthy human liver tissue were established. Serum was collected from a total of 81 PSC patients and 42 healthy controls and tested for reactivity against biliary epithelial cells using flow cytometry. Patient characteristics were correlated with experimental findings.
The results showed that a majority of investigated PSC patients had autoreactive IgA against biliary epithelial cells, whereas these antibodies were almost absent in healthy individuals. Presence of autoreactive IgA in the PSC patients was not associated to gender, age, duration of disease, concomitant inflammatory bowel disease, or cholangiocarcinoma. Instead, the levels of autoreactive IgA correlated with higher total serum IgA levels and autoreactive IgA-positive patients progressed faster to a clinical endpoint (death or liver transplantation) compared to autoreactive IgA-negative patients.
The findings provide new insights into the role of IgA in PSC patients and opens up for future studies addressing pathogenic mechanisms of autoantibodies directed against biliary epithelial cells.
原发性硬化性胆管炎（PSC）是一种以胆管系统进行性破坏为特征的慢性肝病。有研究表明自身免疫反应在PSC的病因和发病机制中起作用，并且在PSC患者中已报道了大量不同的自身抗体。然而，作为胆汁中主要免疫球蛋白并通过胆管上皮细胞转运至胆汁中的IgA在PSC中的作用仍未完全明确。本研究的目的是评估PSC患者中自身反应性IgA的存在情况。
建立来自健康人肝组织的胆管上皮细胞培养物。收集了总共81例PSC患者和42例健康对照者的血清，并使用流式细胞术检测其对胆管上皮细胞的反应性。将患者特征与实验结果进行关联分析。
结果显示，大多数被研究的PSC患者具有针对胆管上皮细胞的自身反应性IgA，而这些抗体在健康个体中几乎不存在。PSC患者中自身反应性IgA的存在与性别、年龄、病程、合并炎症性肠病或胆管癌无关。相反，自身反应性IgA水平与较高的血清总IgA水平相关，并且与自身反应性IgA阴性患者相比，自身反应性IgA阳性患者更快进展至临床终点（死亡或肝移植）。
这些发现为IgA在PSC患者中的作用提供了新的见解，并为未来研究针对胆管上皮细胞的自身抗体的致病机制开辟了道路。
