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. 2022 Nov 3;12(11):2682.
doi: 10.3390/diagnostics12112682.

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

Steffi Lopens  1   2 , Ewa Wunsch  3 , Malgorzata Milkiewicz  4 , Nadja Röber  5 , Grit Zarske  2 , Abdullah Nasser  2 , Karsten Conrad  5 , Martin Laass  6 , Stefan Rödiger  1   7 , Marcin Krawczyk  8   9   10 , Dirk Roggenbuck  1   7 , Piotr Milkiewicz  3   9   11
Affiliations

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

Steffi Lopens et al. Diagnostics (Basel). .

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.

Keywords: antibodies against serine protease proteinase-3; disease severity; health-related quality of life; liver biochemistry; primary sclerosing cholangitis; survival.

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Conflict of interest statement

E.W., M.K., M.M., P.M., K.C. and S.R. declare no conflicts of interest and that there was no pertinent financial arrangement. DRo is an employee and owns shares of GA Generic Assays and Medipan GmbH, which are in vitro diagnostic manufacturers. S.L., A.N., and G.Z. are employees of Medipan GmbH.

Figures

Figure A1
Figure A1
Receiver-operating characteristic curve analysis of PR3-ANCA measurements by a third-generation ELISA using 309 patients with primary sclerosing cholangitis as a disease cohort (positive criterion) and 51 patients with primary biliary cholangitis as well as 120 blood donors as a control cohort (negative criterion). The area under the curve was 0.727 (95% confidential interval: 0.683–0.772, p < 0.0001).
Figure 1
Figure 1
PR3-ANCA levels by third-generation ELISA in sera of 309 patients with primary sclerosing cholangitis (PSC), 51 patients with primary biliary cholangitis (PBC) and 120 blood donors. Data are displayed as units per milliliter in box-and-whisker plots with far out values defined as values that are smaller than the lower quartile minus three times the interquartile range or larger than the upper quartile plus three times the interquartile range, displayed as solid red triangles. The recommended cut-off of 15 U/mL is indicated as a horizontal dashed black line. * p < 0.05, Kruskal–Wallis test with Conover’s post hoc analysis.
Figure 2
Figure 2
Kaplan–Meier survival curve for 309 patients with primary sclerosing cholangitis, depending on PR3-ANCA status.
See this image and copyright information in PMC

References

    1. Karlsen T.H., Folseraas T., Thorburn D., Vesterhus M. Primary sclerosing cholangitis—A comprehensive review. J. Hepatol. 2017;67:1298–1323. doi: 10.1016/j.jhep.2017.07.022. - DOI - PubMed
    1. Weismüller T.J., Trivedi P.J., Bergquist A., Imam M., Lenzen H., Ponsioen C.Y., Holm K., Gotthardt D., Färkkilä M., Marschall H.-U., et al. Patient Age, Sex, and Inflammatory Bowel Disease Phenotype Associate With Course of Primary Sclerosing Cholangitis. Gastroenterology. 2017;152:1975–1984.e8. doi: 10.1053/j.gastro.2017.02.038. - DOI - PMC - PubMed
    1. Boberg K.M., Bergquist A., Mitchell S., Pares A., Rosina F., Broomé U., Chapman R., Fausa O., Egeland T., Rocca G., et al. Cholangiocarcinoma in Primary Sclerosing Cholangitis: Risk Factors and Clinical Presentation. Scand. J. Gastroenterol. 2002;37:1205–1211. doi: 10.1080/003655202760373434. - DOI - PubMed
    1. Lopens S., Krawczyk M., Papp M., Milkiewicz P., Schierack P., Liu Y., Wunsch E., Conrad K., Roggenbuck D. The search for the Holy Grail: Autoantigenic targets in primary sclerosing cholangitis associated with disease phenotype and neoplasia. Autoimmun. Highlights. 2020;11:6. doi: 10.1186/s13317-020-00129-x. - DOI - PMC - PubMed
    1. Weismüller T.J., Wedemeyer J., Kubicka S., Strassburg C.P., Manns M.P. The challenges in primary sclerosing cholangitis—Aetiopathogenesis, autoimmunity, management and malignancy. J. Hepatol. 2008;48((Suppl. S1)):S38–S57. doi: 10.1016/j.jhep.2008.01.020. - DOI - PubMed

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