Lopens Steffi, Wunsch Ewa, Milkiewicz Malgorzata, Röber Nadja, Zarske Grit, Nasser Abdullah, Conrad Karsten, Laass Martin, Rödiger Stefan, Krawczyk Marcin, Roggenbuck Dirk, Milkiewicz Piotr
Institute of Biotechnology, Faculty Environment and Natural Sciences, Brandenburg University of Technology Cottbus-Senftenberg, 01968 Senftenberg, Germany.
Medipan GmbH, 15827 Dahlewitz, Germany.
Diagnostics (Basel). 2022 Nov 3;12(11):2682. doi: 10.3390/diagnostics12112682.
A highly sensitive detection of anti-neutrophil cytoplasmic antibodies to serine proteinase-3 (PR3-ANCAs) aids in the serological diagnosis of autoimmune liver disorders and the prediction of severity in primary sclerosing cholangitis (PSC). Here, we evaluate a novel third-generation ELISA for the detection of PR3-ANCAs. In total, 309 patients with PSC, 51 with primary biliary cholangitis (PBC), and 120 healthy blood donors (BD) were analyzed. For the survival analysis in PSC, the outcome was defined as liver-transplantation-free survival during the follow-up. Positive PR3-ANCA levels were found in 74/309 (24.0%) of patients with PSC. No BDs and one patient with PBC demonstrated PR3-ANCA positivity. PR3-ANCAs were revealed as independent predictors for a poor PSC outcome (study endpoint: liver transplantation/death, log-rank test, p = 0.02). PR3-ANCA positivity, lower albumin levels, and higher bilirubin concentrations were independent risks of a poor survival (Cox proportional-hazards regression analysis, p < 0.05). The Mayo risk score for PSC was associated with PR3-ANCA positivity (p = 0.01) and the disease severity assessed with a model of end-stage liver disease (MELD) and extended MELD-Na (p < 0.05). PR3-ANCAs detected by a third-generation ELISA are diagnostic and prognostic markers for PSC. Their wider use could help to identify patients who are at-risk of a more severe disease.
对丝氨酸蛋白酶3抗中性粒细胞胞浆抗体（PR3-ANCA）的高灵敏度检测有助于自身免疫性肝病的血清学诊断以及原发性硬化性胆管炎（PSC）严重程度的预测。在此，我们评估一种用于检测PR3-ANCA的新型第三代酶联免疫吸附测定（ELISA）。总共分析了309例PSC患者、51例原发性胆汁性胆管炎（PBC）患者和120名健康献血者（BD）。对于PSC的生存分析，结局定义为随访期间无肝移植生存。在309例PSC患者中有74例（24.0%）PR3-ANCA水平呈阳性。没有BD显示PR3-ANCA阳性，1例PBC患者PR3-ANCA呈阳性。PR3-ANCA被揭示为PSC不良结局的独立预测因素（研究终点：肝移植/死亡，对数秩检验，p = 0.02）。PR3-ANCA阳性、较低的白蛋白水平和较高的胆红素浓度是生存不良的独立风险因素（Cox比例风险回归分析，p < 0.05）。PSC的梅奥风险评分与PR3-ANCA阳性相关（p = 0.01），并且与用终末期肝病模型（MELD）和扩展MELD-Na评估的疾病严重程度相关（p < 0.05）。通过第三代ELISA检测的PR3-ANCA是PSC的诊断和预后标志物。它们的更广泛应用可能有助于识别有更严重疾病风险的患者。
