Murota M, Nishioka M, Fujita J, Dobashi N, Wu F, Ohtsuki Y, Hojo S, Takahara J, Kuriyama S
Third Department of Internal Medicine, Kagawa Medical University, Kagawa, Japan.
Clin Exp Immunol. 2001 Aug;125(2):291-9. doi: 10.1046/j.1365-2249.2001.01568.x.
Antibodies to cytokeratin (CK) are found in some patients with autoimmune hepatitis (AIH). We hypothesized that serum antibodies to CK8, CK18 and CK19 may be formed in patients with AIH. We established an enzyme-linked immunosorbent assay (ELISA) to quantify anti-CK8, anti-CK18 and anti-CK19 antibodies in sera of patients with AIH. In addition, we quantified circulating CK8:anti-CK8 antibody as well as CK18:anti-CK18 antibody immune complexes in patients' sera, by an enzyme-linked immunosorbent assay (ELISA). Furthermore, to evaluate the expression of CK8, CK18 and CK19 in liver tissue, immunohistochemical stainings were performed. Significantly high levels of anti-CK8, anti-CK18 and anti-CK19 antibodies were demonstrated in patients with AIH compared with normal volunteers and patients with chronic active hepatitis C (CH-C). In addition, these antibodies were significantly decreased after steroid treatment. Levels of CK8:anti-CK8 and CK18:anti-CK18 immune complexes in sera of patients with AIH were significantly high compared with those of patients with CH-C and normal volunteers. Immunohistochemically, CK8 or CK18 were absent from some hepatocytes of AIH. CK19 was aberrantly expressed in periportal hepatocytes in patients with AIH, but not CH-C. This is the first study to quantify anti-CK8, anti-CK18, anti-CK19 antibodies and immune complexes in patients with AIH. The clinical significance of anti-CK antibodies and their immune complexes of AIH is also discussed.
在一些自身免疫性肝炎(AIH)患者中可发现细胞角蛋白(CK)抗体。我们推测AIH患者体内可能会形成针对CK8、CK18和CK19的血清抗体。我们建立了一种酶联免疫吸附测定(ELISA)法来定量检测AIH患者血清中的抗CK8、抗CK18和抗CK19抗体。此外,我们还通过酶联免疫吸附测定(ELISA)法对患者血清中循环的CK8:抗CK8抗体以及CK18:抗CK18抗体免疫复合物进行了定量分析。此外,为评估CK8、CK18和CK19在肝组织中的表达情况,我们进行了免疫组织化学染色。与正常志愿者和慢性丙型肝炎(CH-C)患者相比,AIH患者体内抗CK8、抗CK18和抗CK19抗体水平显著升高。此外,这些抗体在类固醇治疗后显著降低。与CH-C患者和正常志愿者相比,AIH患者血清中CK8:抗CK8和CK18:抗CK18免疫复合物水平显著升高。免疫组织化学结果显示,AIH患者的一些肝细胞中不存在CK8或CK18。CK19在AIH患者的汇管区周围肝细胞中异常表达,但在CH-C患者中未出现这种情况。这是第一项对AIH患者的抗CK8、抗CK18、抗CK19抗体及免疫复合物进行定量分析的研究。同时,我们还讨论了AIH患者抗CK抗体及其免疫复合物的临床意义。