A novel serum metabolomic panel distinguishes IgG4‐related sclerosing cholangitis from primary sclerosing cholangitis

Abstract

Background & Aims: Primary 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. Methods: We 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). Results: Multivariate 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 -CH 3 lipoprotein resonances (p < .01) were decreased.Conclusions: Taken 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.

Inflammasome and pyroptosis in autoimmune liver diseases

“…There are potential links between microbial or metabolic features in PSC and cholestatic parameters, while disease-related genera and metabolites in IgG4-SC tend to be associated with transaminases of hepatocyte injury. According to the results of recent studies, liver inflammation of IgG4-SC may be responsible for the marked reduction in Blautia and elevation of succinate ( 167 ). However, further research is required to determine the function of inflammasomes in hepatocyte pyroptosis in IgG4-SC.…”

Sodium fluoride preserves blood metabolite integrity for biomarker discovery in large-scale, multi-site metabolomics investigations

“…1 Nuclear magnetic resonance (NMR)-based metabolomics techniques involve the simultaneous profiling of many metabolites (small molecular intermediates) in a biofluid or other medium. 2 Inexpensive, high-throughput, and highly reproducible, global metabolite quantification by NMR is now being employed at the frontier of medicine, ranging from population-wide health profiling 3,4 to predicting diagnosis, 5 progression, 6 and response to treatment 7 in a spectrum of diseases.…”

Distinct metabolomic and lipidomic profiles in serum samples of patients with primary sclerosing cholangitis

“…In summary, some data on prognosis, genetic alterations, and pathogenesis of PSC patients have been obtained in recent years ( 14 – 27 ). However, studies on the metabolome and lipidome of PSC patients are still a rarity ( 11 , 28 – 30 ). We hope that our work will enable us to develop metabolomic profiles for PSC, which will increase the diagnostic accuracy of the diagnosis.…”