Muratori L, Lenzi M, Ma Y, Cataleta M, Mieli-Vergani G, Vergani D, Bianchi F B
Cattedra di Medicina Interna, Policlinico S Orsola, Bologna, Italy.
Gut. 1995 Sep;37(3):406-12. doi: 10.1136/gut.37.3.406.
Liver/kidney microsomal antibody type 1 (LKM-1), the serological marker of a subset of autoimmune hepatitis, is also present in a proportion of patients with hepatitis C virus (HCV) related chronic liver disease. To characterise further this autoreactivity and to evaluate whether an autoantibody giving an identical immunofluorescence staining, and detected in two different clinical conditions, involves the same antigenic target(s), sera from autoimmune and HCV infected patients were tested with native, recombinant, and synthetic antigens. Sixty five sera were selected on the basis of the typical immunofluorescence pattern: 50 patients had serological markers of HCV infection, the remaining 15 suffered from autoimmune hepatitis. The reactivity of each serum with rat and human microsomal fractions, full length human recombinant CYP2D6, and two synthetic peptides spanning the amino acid regions 257-269 and 373-398 of CYP2D6 was systematically investigated by immunoblotting. Fourteen (93%) sera from autoimmune hepatitis patients and 39 (78%) from HCV infected patients reacted with rat and/or human microsomal polypeptides of 39 kD, 50 kD, 58 kD, and 66 kD in different associations, the 50 kD band being the most frequently observed. Reactivity to CYP2D6 and its amino acid sequence 257-269 was significantly more common in autoimmune hepatitis than in HCV infected patients (p < 0.001 and p < 0.0003, respectively). LKM-1 reactivity is directed against heterogeneous and not entirely defined autoantigens. The main target in autoimmune sera is CYP2D6 and its 257-269 amino acid region, while sera from patients with HCV infection are more likely to recognise other microsomal targets, the molecular identity of which is currently unknown.
1型肝肾微粒体抗体（LKM-1）是自身免疫性肝炎一个亚群的血清学标志物，在一部分丙型肝炎病毒（HCV）相关慢性肝病患者中也存在。为了进一步明确这种自身反应性，并评估在两种不同临床情况下检测到的呈现相同免疫荧光染色的自身抗体是否涉及相同的抗原靶点，用天然、重组和合成抗原对自身免疫性和HCV感染患者的血清进行了检测。根据典型的免疫荧光模式选择了65份血清：50例患者有HCV感染的血清学标志物，其余15例患有自身免疫性肝炎。通过免疫印迹系统地研究了每份血清与大鼠和人微粒体组分、全长人重组CYP2D6以及跨越CYP2D6氨基酸区域257 - 269和373 - 398的两种合成肽的反应性。14份（93%）自身免疫性肝炎患者的血清和39份（78%）HCV感染患者的血清与39 kD、50 kD、58 kD和66 kD的大鼠和/或人微粒体多肽以不同组合发生反应，其中50 kD条带最常出现。自身免疫性肝炎患者对CYP2D6及其氨基酸序列257 - 269的反应性明显比HCV感染患者更常见（分别为p < 0.001和p < 0.0003）。LKM-1反应性针对的是异质性且尚未完全明确的自身抗原。自身免疫血清中的主要靶点是CYP2D6及其257 - 269氨基酸区域，而HCV感染患者的血清更有可能识别其他微粒体靶点，其分子身份目前尚不清楚。
