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PR3-ANCA: a promising biomarker in primary sclerosing cholangitis (PSC).

Stinton LM, Bentow C, Mahler M, Norman GL, Eksteen B, Mason AL, Kaplan GG, Lindkvist B, Hirschfield GM, Milkiewicz P, Cheung A, Janssen HL, Fritzler MJ - PLoS ONE (2014)

Bottom Line: PR3-ANCA in PSC patients was not associated with the presence or type of underlying IBD, and, in fact, it was more frequent in Crohn's disease (CD) patients with PSC than previously reported in CD alone.PR3-ANCA is detected in a significant proportion of PSC patients compared to other liver diseases including PBC and AIH.PR3-ANCA is associated with higher liver enzyme levels in PSC, and is not solely related to underlying IBD.

View Article: PubMed Central - PubMed

Affiliation: Department of Medicine, University of Calgary, Calgary, Alberta, Canada.

ABSTRACT

Background and aims: The only recognized biomarker for primary sclerosing cholangitis (PSC) is atypical anti-neutrophil cytoplasmic antibodies (aANCA), which, in addition to having low sensitivity and specificity, is an indirect immunofluorescence (IIF) test lacking the advantages of high throughput and objectivity. Recent reports have shown that antibodies to proteinase-3 (PR3-ANCA) might add diagnostic value in inflammatory bowel disease (IBD), specifically in ulcerative colitis (UC). As PSC is associated with IBD, the objective of this study was to evaluate the frequency and clinical significance of PR3-ANCA in a large cohort of patients.

Methods: A total of 244 PSC and 254 control [autoimmune hepatitis (AIH), primary biliary cirrhosis (PBC), hepatitis C viral infection (HCV), hepatitis B viral infection (HBV), and healthy controls] sera and their clinical correlations were retrospectively analyzed for PR3-ANCA determined by ELISA and a new chemiluminescence immunoassay (CIA). Testing was also performed for aANCA by IIF.

Results: When measured by CIA, PR3-ANCA was detected in 38.5% (94/244) of PSC patients compared to 10.6% (27/254) controls (p<0.0001). By ELISA, PR3-ANCA was detected in 23.4% (57/244) of PSC patients compared to 2.7% (6/254) controls (p<0.0001). PR3-ANCA in PSC patients was not associated with the presence or type of underlying IBD, and, in fact, it was more frequent in Crohn's disease (CD) patients with PSC than previously reported in CD alone. PR3-ANCA in PSC measured by CIA correlated with higher liver enzymes.

Conclusion: PR3-ANCA is detected in a significant proportion of PSC patients compared to other liver diseases including PBC and AIH. PR3-ANCA is associated with higher liver enzyme levels in PSC, and is not solely related to underlying IBD.

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Related in: MedlinePlus

Comparative receiver operating characteristic (ROC) curves analysis.Comparative ROC analysis is shown for PR3-ANCA by ELISA, chemiluminescence immunoassay (CIA) and ANCA by indirect immunofluorescence (pANCA). Primary sclerosing cholangitis (PSC) vs. all liver controls (a) and vs. autoimmune hepatitis (AIH) (b), and vs. primary biliary cirrhosis (PBC) (c). Area under the curve (AUC) and 95% Confidence Intervals (CI) values for the individual assays are presented in the figure.
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pone-0112877-g001: Comparative receiver operating characteristic (ROC) curves analysis.Comparative ROC analysis is shown for PR3-ANCA by ELISA, chemiluminescence immunoassay (CIA) and ANCA by indirect immunofluorescence (pANCA). Primary sclerosing cholangitis (PSC) vs. all liver controls (a) and vs. autoimmune hepatitis (AIH) (b), and vs. primary biliary cirrhosis (PBC) (c). Area under the curve (AUC) and 95% Confidence Intervals (CI) values for the individual assays are presented in the figure.

Mentions: ROC curves were used to test the ability of the serological tests to discriminate PSC from other liver controls (Figure 1). When PSC was compared to all controls the area under the curve (AUC) values were 0.67 (CIA), 0.78 (ELISA), and 0.69 (IIF), respectively. When PSC was compared to AIH the area under the curve (AUC) values were 0.56 (CIA), 0.68 (ELISA), and 0.52 (IIF), respectively. When PSC was compared to PBC the area under the curve (AUC) values were 0.60 (CIA), 0.81 (ELISA), and 0.75 (IIF), respectively.


PR3-ANCA: a promising biomarker in primary sclerosing cholangitis (PSC).

Stinton LM, Bentow C, Mahler M, Norman GL, Eksteen B, Mason AL, Kaplan GG, Lindkvist B, Hirschfield GM, Milkiewicz P, Cheung A, Janssen HL, Fritzler MJ - PLoS ONE (2014)

Comparative receiver operating characteristic (ROC) curves analysis.Comparative ROC analysis is shown for PR3-ANCA by ELISA, chemiluminescence immunoassay (CIA) and ANCA by indirect immunofluorescence (pANCA). Primary sclerosing cholangitis (PSC) vs. all liver controls (a) and vs. autoimmune hepatitis (AIH) (b), and vs. primary biliary cirrhosis (PBC) (c). Area under the curve (AUC) and 95% Confidence Intervals (CI) values for the individual assays are presented in the figure.
© Copyright Policy
Related In: Results  -  Collection

License
Show All Figures
getmorefigures.php?uid=PMC4232573&req=5

pone-0112877-g001: Comparative receiver operating characteristic (ROC) curves analysis.Comparative ROC analysis is shown for PR3-ANCA by ELISA, chemiluminescence immunoassay (CIA) and ANCA by indirect immunofluorescence (pANCA). Primary sclerosing cholangitis (PSC) vs. all liver controls (a) and vs. autoimmune hepatitis (AIH) (b), and vs. primary biliary cirrhosis (PBC) (c). Area under the curve (AUC) and 95% Confidence Intervals (CI) values for the individual assays are presented in the figure.
Mentions: ROC curves were used to test the ability of the serological tests to discriminate PSC from other liver controls (Figure 1). When PSC was compared to all controls the area under the curve (AUC) values were 0.67 (CIA), 0.78 (ELISA), and 0.69 (IIF), respectively. When PSC was compared to AIH the area under the curve (AUC) values were 0.56 (CIA), 0.68 (ELISA), and 0.52 (IIF), respectively. When PSC was compared to PBC the area under the curve (AUC) values were 0.60 (CIA), 0.81 (ELISA), and 0.75 (IIF), respectively.

Bottom Line: PR3-ANCA in PSC patients was not associated with the presence or type of underlying IBD, and, in fact, it was more frequent in Crohn's disease (CD) patients with PSC than previously reported in CD alone.PR3-ANCA is detected in a significant proportion of PSC patients compared to other liver diseases including PBC and AIH.PR3-ANCA is associated with higher liver enzyme levels in PSC, and is not solely related to underlying IBD.

View Article: PubMed Central - PubMed

Affiliation: Department of Medicine, University of Calgary, Calgary, Alberta, Canada.

ABSTRACT

Background and aims: The only recognized biomarker for primary sclerosing cholangitis (PSC) is atypical anti-neutrophil cytoplasmic antibodies (aANCA), which, in addition to having low sensitivity and specificity, is an indirect immunofluorescence (IIF) test lacking the advantages of high throughput and objectivity. Recent reports have shown that antibodies to proteinase-3 (PR3-ANCA) might add diagnostic value in inflammatory bowel disease (IBD), specifically in ulcerative colitis (UC). As PSC is associated with IBD, the objective of this study was to evaluate the frequency and clinical significance of PR3-ANCA in a large cohort of patients.

Methods: A total of 244 PSC and 254 control [autoimmune hepatitis (AIH), primary biliary cirrhosis (PBC), hepatitis C viral infection (HCV), hepatitis B viral infection (HBV), and healthy controls] sera and their clinical correlations were retrospectively analyzed for PR3-ANCA determined by ELISA and a new chemiluminescence immunoassay (CIA). Testing was also performed for aANCA by IIF.

Results: When measured by CIA, PR3-ANCA was detected in 38.5% (94/244) of PSC patients compared to 10.6% (27/254) controls (p<0.0001). By ELISA, PR3-ANCA was detected in 23.4% (57/244) of PSC patients compared to 2.7% (6/254) controls (p<0.0001). PR3-ANCA in PSC patients was not associated with the presence or type of underlying IBD, and, in fact, it was more frequent in Crohn's disease (CD) patients with PSC than previously reported in CD alone. PR3-ANCA in PSC measured by CIA correlated with higher liver enzymes.

Conclusion: PR3-ANCA is detected in a significant proportion of PSC patients compared to other liver diseases including PBC and AIH. PR3-ANCA is associated with higher liver enzyme levels in PSC, and is not solely related to underlying IBD.

Show MeSH
Related in: MedlinePlus