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PR3-ANCAs Detected by Third-Generation ELISA Predicts Severe Disease and Poor Survival in Primary Sclerosing Cholangitis

  • 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 riskA 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.show moreshow less

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Author: Steffi Lopens, Ewa Wunsch, Malgorzata Milkiewicz, Nadja Röber, Grit Zarske, Abdullah Nasser, Karsten Conrad, Martin W. Laass, Stefan RödigerORCiD, Marcin Krawczyk, Dirk RoggenbuckORCiD, Piotr Milkiewicz
DOI:https://doi.org/10.3390/diagnostics12112682
ISSN:2075-4418
Title of the source (English):Diagnostics
Document Type:Scientific journal article peer-reviewed
Language:English
Year of publication:2022
Tag:antibodies against serine protease proteinase-3; disease severity; health-related quality of life; liver biochemistry; primary sclerosing cholangitis; survival
Volume/Year:12
Issue number:11
Article number:2682
Way of publication:Open Access
Faculty/Chair:Fakultät 2 Umwelt und Naturwissenschaften / FG Multiparameterdiagnostik
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