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PR3-ANCAs Detected by Third-Generation ELISA Predicts Severe Disease and Poor Survival in Primary Sclerosing
Steffi Lopens1,2, Ewa Wunsch3, Malgorzata Milkiewicz4
1Institute of Biotechnology, Faculty Environment and Natural Sciences, Brandenburg University of Technology Cottbus-Senftenberg, 01968 Senftenberg, Germany.
Insights
A new ELISA test accurately detects anti-neutrophil cytoplasmic antibodies to serine proteinase-3 (PR3-ANCAs), identifying severe primary sclerosing cholangitis (PSC) and predicting patient outcomes.
Area of Science:
- Immunology
- Hepatology
- Autoimmune Diseases
Background:
- Anti-neutrophil cytoplasmic antibodies to serine proteinase-3 (PR3-ANCAs) are implicated in autoimmune liver disorders.
- Primary sclerosing cholangitis (PSC) is a chronic liver disease with variable severity and prognosis.
Purpose of the Study:
- To evaluate a novel third-generation ELISA for PR3-ANCA detection.
- To assess the diagnostic and prognostic value of PR3-ANCAs in PSC patients.
Main Methods:
- Analysis of 309 PSC patients, 51 primary biliary cholangitis (PBC) patients, and 120 healthy blood donors (BD).
- Third-generation ELISA used for PR3-ANCA detection.
- Survival analysis using liver-transplantation-free survival, log-rank test, and Cox regression.
Main Results:
- 24.0% of PSC patients were PR3-ANCA positive; only one PBC patient and no BDs were positive.
- PR3-ANCAs independently predicted poor PSC outcomes (liver transplantation/death, p=0.02).
- PR3-ANCA positivity, low albumin, and high bilirubin were risks for poor survival (p<0.05).
Conclusions:
- Third-generation ELISA-detected PR3-ANCAs are valuable diagnostic and prognostic markers for PSC.
- Wider use of PR3-ANCA testing can identify high-risk PSC patients.
- PR3-ANCA positivity correlates with PSC severity scores (Mayo, MELD, MELD-Na).
Abstract:
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.
