Association between serum IgE level and adverse clinical endpoints in primary sclerosing cholangitis

Abstract

Introduction Primary sclerosing cholangitis (PSC) is an idiopathic hepatobiliary disorder associated with an increased risk for cholangiocarcinoma (CCA) and a median survival time of 12 years. Reliable predictors of CCA and other major adverse events in PSC are currently lacking. Recently, serum IgE was found to be associated with CCA in a Japanese cohort of PSC patients. Our aim in this study was to determine whether IgE levels predict time to CCA, liver transplantation, or death in a Western (USA-based) cohort of PSC patients. Material and methods Thirty-eight patients with PSC and IgE levels were identified and categorized into low or high IgE groups based on the sample median. Groups were compared with respect to clinical characteristics and adverse endpoint-free survival, and the association between IgE and endpoints was assessed with multivariate proportional-hazards models. Results The median sample age at PSC diagnosis was 41 years, and median serum IgE level was 47.6 kU/L. Low and high IgE groups differed significantly only with respect to IgG subclasses, which were higher among the latter (p < 0.05). There were no significant differences in composite endpoint-free (p = 0.83) or CCA-free survival (p = 0.20). In multivariate analyses, only Mayo PSC risk score and MELD score were significant predictors of endpoint-free survival (p < 0.05). Conclusions Serum IgE level is associated with several IgG subclass levels but not time to CCA, liver transplantation, or death among PSC patients in a USA-based cohort. While Mayo PSC risk score and MELD score can predict these outcomes, more specific predictors of CCA are needed.

Primary sclerosing cholangitis: A review and update

“…50–53 Patients with an increase in one immunoglobulin isotype will generally also have elevations of other isotypes. 53 The significance of hyperglobulinemias in PSC remains unclear.…”

“…50–53 Patients with an increase in one immunoglobulin isotype will generally also have elevations of other isotypes. 53 The significance of hyperglobulinemias in PSC remains unclear. In a study of Japanese patients with PSC, high serum IgE levels were negatively associated with developing CCA; 51 this finding was not replicated, however, in a US-based cohort.…”

“…In a study of Japanese patients with PSC, high serum IgE levels were negatively associated with developing CCA; 51 this finding was not replicated, however, in a US-based cohort. 53 …”

“…Therefore, while useful for research purposes, their clinical utility is unclear. 6 More recently, the MELD score was developed to identify patients (PSC and non-PSC) at highest mortality risk and determine organ allocation priority; 113 though capable of estimating survival, 53 as with the Mayo model, its clinical use (aside from planning potential LT) is limited. Recently, serum ALP improvement or normalization has been shown to be associated with decreased risk of major adverse PSC-related events and is under continued investigation as a potential prognostic biomarker.…”

Duration of Inflammatory Bowel Disease Is Associated With Increased Risk of Cholangiocarcinoma in Patients With Primary Sclerosing Cholangitis and IBD

“…The risk factors for CCA in PSC have been reported, although none are sufficiently robust or reliable enough to alter recommendations for disease surveillance (6,7). As a consequence, major international societies have not made specific recommendations for surveillance of CCA in patients with PSC, but acknowledge that, given the prognostic implications of this diagnosis, many clinicians will offer surveillance with an imaging study and carbohydrate antigen 19-9 (CA 19-9) at yearly intervals (8,9).…”