A novel serum metabolomic panel distinguishes IgG4‐related sclerosing cholangitis from primary sclerosing cholangitis
Radford‐Smith DE., Selvaraj EA., Peters R., Orrell M., Bolon J., Anthony DC., Pavlides M., Lynch K., Geremia A., Bailey A., Culver EL., Probert F.
AbstractBackground & AimsPrimary sclerosing cholangitis (PSC) and IgG4‐related sclerosing cholangitis (IgG4‐SC) are chronic fibro‐inflammatory immune‐mediated hepatobiliary conditions that are challenging to distinguish in a clinical setting. Accurate non‐invasive biomarkers for discriminating PSC and IgG4‐SC are important to ensure a correct diagnosis, prompt therapy and adequate cancer surveillance.MethodsWe performed nuclear magnetic resonance (NMR)‐based metabolomic profiling using serum samples collected prospectively from patients with PSC (n = 100), IgG4‐SC (n = 23) and healthy controls (HC; n = 16).ResultsMultivariate analysis of the serum metabolome discriminated PSC from IgG4‐SC with greater accuracy (AUC 0.95 [95%CI 0.90–0.98]) than IgG4 titre (AUC 0.87 [95%CI 0.79–0.94]). When inflammatory bowel disease (IBD) was excluded as a comorbid condition (IgG4‐SC n = 20, PSC n = 22), the diagnostic AUC increased to 1.0, suggesting that the metabolome differences identified are not a result of the increased prevalence of IBD in PSC relative to IgG4‐SC patients. Serum lactate (p < .0001), glucose (p < .01) and glutamine (p < .01) metabolites were increased in IgG4‐related disease (IgG4‐RD) and IgG4‐SC individuals compared to PSC, whereas mobile choline (p < .05), 3‐hydroxybutyric acid (p < .01) and ‐CH3 lipoprotein resonances (p < .01) were decreased.ConclusionsTaken together, serum metabolomic profiling has the potential to be incorporated as a diagnostic criterion, independent of IgG4 titre, to improve the diagnosis of IgG4‐RD and help distinguish IgG4‐SC from PSC.