Cytochrome P450 1A2 is a hepatic autoantigen in autoimmune polyglandular syndrome type 1
Cytochrome P450 1A2 is a hepatic autoantigen in autoimmune polyglandular syndrome type 1
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DOI：
10.1210/jc.82.5.1353
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发表时间：
1997-05-01
影响因子：
5.8
通讯作者：
Manns, MP
中科院分区：
文献类型：
--
作者：
Clemente, MG;ObermayerStraub, P;Manns, MP
在 88 名撒丁岛后裔受试者中研究了针对肾上腺皮质和肝脏蛋白质的自身抗体。即 6 名自身免疫性多内分泌综合征 1 型（APS1）患者、22 名 APS1 患者亲属、40 名患有其他自身免疫性疾病的对照者和 20 名健康对照者。间接免疫荧光，使用肾上腺皮质的组织切片。揭示了 6 名 APS1 患者中的 4 名的细胞质染色模式。肾上腺线粒体蛋白质印迹鉴定出 54 kDa 和 57 kDa 的自身抗原，胎盘线粒体蛋白质印迹发现 54 kDa 自身抗原。 6 名 APS1 患者中的 4 名在胎盘和肾上腺组织中都能识别出 54-kDa 蛋白，而 57-kDa 蛋白仅在一名血清中被检测到。使用细胞色素P450蛋白的重组制剂，将自身抗原鉴定为P450 sec和P450 c17。六名APS1患者中的一名患有慢性肝炎。在该患者中，免疫荧光显示小叶中心肝脏和近端肾小管染色模式。使用人肝脏微粒体制剂进行的蛋白质印迹显示出 52 kDa 的蛋白质条带。通过使用重组蛋白制剂，将自身抗原鉴定为细胞色素P450 1A2。 P450 1A2 代表 APS1 中报道的第一个肝自身抗原。 P450 1A2 通常不会在孤立性自身免疫性肝病患者的血清中检测到，并且可能是 APS1 患者的肝脏标志物自身抗原。
Autoantibodies directed against proteins of the adrenal cortex and the liver were studied in 88 subjects of Sardinian descent. namely six patients with autoimmune polyendocrine syndrome type 1(APS1), 22 relatives of APS1 patients, 40 controls with other autoimmune diseases, and 20 healthy controls. Indirect immunofluorescence, using tissue sections of the adrenal cortex. revealed a cytoplasmatic staining pattern in 4 of 6 patients with APS1. Western blotting with adrenal mitochondria identified autoantigens of 54 kDa and 57 kDa, Western blotting with placental mitochondria revealed a 54-kDa autoantigen. The 54-kDa protein was recognized by 4 of 6 patients with APS1 both in placental and adrenal tissue, whereas the 57-kDa protein was detected only by one serum. Using recombinant preparations of cytochrome P450 proteins, the autoantigens were identified as P450 sec and P450 c17.One of six APS1 patients suffered from chronic hepatitis. In this patient, immunofluorescence revealed a centrolobular liver and a proximal renal tubule staining pattern. Western blots using microsomal preparations of human liver revealed a protein band of 52 kDa. The autoantigen was identified as cytochrome P450 1A2 by use of recombinant protein preparations. P450 1A2 represents the first hepatic autoantigen reported in APS1. P450 1A2 usually is not detected by sera of patients with isolated autoimmune liver disease and might be a hepatic marker autoantigen for patients with APS1.