Obermayer-Straub P, Perheentupa J, Braun S, Kayser A, Barut A, Loges S, Harms A, Dalekos G, Strassburg C P, Manns M P
Department of Gastroenterology and Hepatology, Hanover Medical School, Germany.
Gastroenterology. 2001 Sep;121(3):668-77. doi: 10.1053/gast.2001.27103.
BACKGROUND & AIMS: Autoimmune polyendocrinopathy-candidiasis-ectodermal dystrophy (APECED) is caused by mutations of both copies of the autoimmune regulator (AIRE) gene. It is characterized by susceptibility to mucocutaneous candidiasis and multiple autoimmune lesions. A serious disease component is hepatitis. To identify diagnostic autoantibodies for APECED hepatitis, sera from 64 patients with APECED were screened for autoantibodies established in the diagnosis of idiopathic autoimmune hepatitis, and for autoantibodies against 10 cytochrome P450s.
Screening methods were indirect immunofluorescence, Western blot, Ouchterlony gel diffusion, enzyme-linked immunosorbent assay, and immunoprecipitation.
Anti-liver microsomal antibodies were detected in 50% of the patients with APECED hepatitis and 11% of those without hepatitis. Prevalences of antinuclear, smooth muscle, anti-liver cytosol, anti-soluble liver protein/liver pancreas, and anti-CYP2D6 autoantibodies were 9%, 6%, 3%, 0%, and 0%, respectively. CYP1A1, CYP2B6, CYP1A2, and CYP2A6 were identified as autoantigens. Thirty percent of patients with anti-CYP2A6 and 100% of patients with anti-CYP1A2 were affected by hepatitis. Despite the high specificity of anti-CYP1A2 for APECED hepatitis, its sensitivity was low (50%). Anti-CYP2A6 and anti-CYP1A2 were not detected in patients with autoimmune hepatitis (N = 68) or nonhepatitic controls (N = 81).
Anti-CYP1A2 is a highly specific but insensitive marker for APECED hepatitis. No clinical correlation was observed for anti-CYP2A6. Autoimmune hepatitis and APECED hepatitis are characterized by different molecular targets of autoantibodies with no overlap.
自身免疫性多内分泌腺病-念珠菌病-外胚层营养不良（APECED）由自身免疫调节因子（AIRE）基因的两个拷贝发生突变引起。其特征为易患黏膜皮肤念珠菌病和多种自身免疫性病变。一种严重的疾病成分是肝炎。为了鉴定APECED肝炎的诊断性自身抗体，对64例APECED患者的血清进行筛查，检测用于诊断特发性自身免疫性肝炎的自身抗体以及针对10种细胞色素P450的自身抗体。
筛查方法包括间接免疫荧光法、蛋白质印迹法、双向琼脂扩散法、酶联免疫吸附测定法和免疫沉淀法。
50%的APECED肝炎患者检测到抗肝微粒体抗体，无肝炎的患者中这一比例为11%。抗核抗体、平滑肌抗体、抗肝细胞溶质抗体、抗可溶性肝蛋白/肝胰抗体和抗CYP2D6自身抗体的患病率分别为9%、6%、3%、0%和0%。CYP1A1、CYP2B6、CYP1A2和CYP2A6被鉴定为自身抗原。30%的抗CYP2A6患者和100%的抗CYP1A2患者患有肝炎。尽管抗CYP1A2对APECED肝炎具有高特异性，但其敏感性较低（50%）。自身免疫性肝炎患者（N = 68）或非肝炎对照者（N = 81）中未检测到抗CYP2A6和抗CYP1A2。
抗CYP1A2是APECED肝炎的高特异性但不敏感的标志物。未观察到抗CYP2A6与临床的相关性。自身免疫性肝炎和APECED肝炎的特征是自身抗体的分子靶点不同，无重叠。
