ANTI-GLYCOPROTEIN 2 AND PR3-ANCA ARE RISK FACTORS OF SEVERE CLINICAL PHENOTYPE, POOR OUTCOME, AND CHOLANGIOCARCINOMA IN PRIMARY SCLEROSING CHOLANGITIS
- Gary L. Norman, United States of America
Abstract
Background and Aims
Anti-glycoprotein 2(anti-GP2) and PR3-ANCA have been linked with primary sclerosing cholangitis(PSC) in which anti-GP2 IgA was suggested as a marker of disease severity and poor survival related to cholangiocarcinoma(CCA) and PR3-ANCA, as a marker of disease severity. Here we assessed anti-GP2 IgA and PR-3 ANCA as predictive factors of progressive disease course and poor outcome in a large cohort of PSC patients.
Methods
338 patients with PSC [median 32(17-73) years, 65% males, 26% cirrhotic] were prospectively evaluated. Anti-GP2 IgA (isoforms 1/4) detected by ELISAs (GA Generic Assays, Germany) and PR3-ANCA by chemiluminescence immunoassay (CIA; Inova Diagnostics, San Diego; optimized cutoff 10 units). Poor disease outcome was defined as liver transplantation and/or liver-related death during the 14 month median follow-up.
Results
Anti-GP21 IgA occurred in 23%, anti-GP24 IgA in 17%, anti-GP21 and/or GP24 IgA in 30%, and PR3-ANCA in 54.5% of patients. Anti-GP2 IgA and PR3-ANCA associated with poor liver function. Cirrhosis was associated with anti-GP24 IgA(p=0.003). CCA occurred more often in patients with anti-GP21 IgA(p=0.04) and PR3-ANCA (p=0.008). 100% of CCA patients were positive for PR3 and/or GP2 IgA. Significant associations between anti-GP21 IgA(Hazzard Ratio, HR=2.1, p=0.0008), anti-GP24 IgA(HR=2.4, p=0.005), and PR3-ANCA(HR=1.8, p=0.009) and poor outcome were found. Cox proportional-hazards regression indicated anti-GP21 IgA and lower albumin level as independent variables of poor outcome (p<0.0001), whereas anti-GP24 IgA and PR3-ANCA were independent risk factors of CCA (p=0.0019).
Conclusions
Anti-GP2 IgA and PR3-ANCA identify PSC patients at risk of poor outcome, more aggressive course, biliary cancer, and may be of prognostic value in PSC.