Terjung B, Bogsch F, Klein R, Söhne J, Reichel C, Wasmuth J-C, Beuers U, Sauerbruch T, Spengler U
Department of Internal Medicine I, University of Bonn, Sigmund-Freud-Strasse 25, D-53105 Bonn, Germany.
Eur J Med Res. 2004 Sep 29;9(9):439-48.
Antineutrophil cytoplasmic antibodies (atypical p-ANCA) are detected at high prevalence in sera from patients with autoimmune hepatitis (AIH), but their diagnostic relevance for AIH has not been systematically evaluated so far.
Here, we studied sera from 357 patients with autoimmune (autoimmune hepatitis n=175, primary sclerosing cholangitis (PSC) n=35, primary biliary cirrhosis n=45), non-autoimmune chronic liver disease (alcoholic liver cirrhosis n=62; chronic hepatitis C virus infection (HCV) n=21) or healthy controls (n=19) for the presence of various non-organ specific autoantibodies. Atypical p-ANCA, antinuclear antibodies (ANA), antibodies against smooth muscles (SMA), antibodies against liver/kidney microsomes (anti-Lkm1) and antimitochondrial antibodies (AMA) were detected by indirect immunofluorescence microscopy, antibodies against the M2 antigen (anti-M2), antibodies against soluble liver antigen (anti-SLA/LP) and anti-Lkm1 by using enzyme linked immunosorbent assays. To define the diagnostic precision of the autoantibodies, results of autoantibody testing were analyzed by receiver operating characteristics (ROC) and forward conditional logistic regression analysis.
Atypical p-ANCA were detected at high prevalence in sera from patients with AIH (81%) and PSC (94%). ROC- and logistic regression analysis revealed atypical p-ANCA and SMA, but not ANA as significant diagnostic seromarkers for AIH (atypical p-ANCA: AUC 0.754+/-0.026, odds ratio [OR] 3.4; SMA: 0.652+/-0.028, OR 4.1). Atypical p-ANCA also emerged as the only diagnostically relevant seromarker for PSC (AUC 0.690+/-0.04, OR 3.4). None of the tested antibodies yielded a significant diagnostic accuracy for patients with alcoholic liver cirrhosis, HCV or healthy controls.
Atypical p-ANCA along with SMA represent a seromarker with high diagnostic accuracy for AIH and should be explicitly considered in a revised version of the diagnostic score for AIH.
抗中性粒细胞胞浆抗体（非典型p-ANCA）在自身免疫性肝炎（AIH）患者血清中的检出率很高，但迄今为止，它们对AIH的诊断相关性尚未得到系统评估。
在此，我们研究了357例自身免疫性疾病（自身免疫性肝炎n = 175、原发性硬化性胆管炎（PSC）n = 35、原发性胆汁性肝硬化n = 45）、非自身免疫性慢性肝病（酒精性肝硬化n = 62；慢性丙型肝炎病毒感染（HCV）n = 21）患者或健康对照（n = 19）的血清中各种非器官特异性自身抗体的存在情况。通过间接免疫荧光显微镜检测非典型p-ANCA、抗核抗体（ANA）、抗平滑肌抗体（SMA）、抗肝肾微粒体抗体（抗-Lkm1）和抗线粒体抗体（AMA），通过酶联免疫吸附试验检测抗M2抗原抗体（抗-M2）、抗可溶性肝抗原抗体（抗-SLA/LP）和抗-Lkm1。为了确定自身抗体的诊断准确性，通过受试者工作特征（ROC）和向前条件逻辑回归分析来分析自身抗体检测结果。
非典型p-ANCA在AIH患者（81%）和PSC患者（94%）的血清中检出率很高。ROC和逻辑回归分析显示，非典型p-ANCA和SMA而非ANA是AIH的重要诊断血清标志物（非典型p-ANCA：曲线下面积（AUC）0.754±0.026，比值比[OR]3.4；SMA：0.652±0.028，OR 4.1）。非典型p-ANCA也是PSC唯一具有诊断相关性的血清标志物（AUC 0.690±0.04，OR 3.4）。对于酒精性肝硬化、HCV患者或健康对照，所检测的抗体均未产生显著的诊断准确性。
非典型p-ANCA与SMA一起是AIH诊断准确性高的血清标志物，应在AIH诊断评分的修订版中明确考虑。
