Clinical Utility of Personalized Serum IgG Subclass Ratios for the Differentiation of IgG4-Related Sclerosing Cholangitis (IgG4-SC) from Primary Sclerosing Cholangitis (PSC) and Cholangiocarcinoma (CCA)

Background: The differential diagnosis of immunoglobulin G4-sclerosing cholangitis (IgG4-SC) from primary sclerosing cholangitis (PSC) or cholangiocarcinoma (CCA) is important. In this study, we aimed to find the best combinations of serum IgG subclasses and IgG4 levels for differentiating IgG4-SC from PSC or CCA. Methods: In total, 31 patients with IgG4-SC, 27 patients with PSC, and 40 patients with CCA were enrolled from 2003 to 2017 at a single tertiary referral center. We retrospectively assessed the IgG4, IgG4/IgG1, IgG4/(IgG1+IgG3), and (IgG4+IgG2)/(IgG1+IgG3) in each of the patients. ROC curves were established to obtain the optimal cutoff value for each parameter. McNemar's test was used to compare the sensitivities, specificities, and accuracies of diagnostic algorithms. Results: In differentiating IgG4-SC from PSC, the accuracies of IgG4/IgG1 >= 0.087 and of IgG4/(IgG1+IgG3) >= 0.081 were significantly higher than that of IgG4 >= 135 mg/dL alone (78% vs. 66%, p = 0.025). Serum IgG4 >= 52 mg/dL showed the best accuracy for differentiation of IgG4-SC from CCA, with a sensitivity and specificity of 80% and 82%, respectively, but this was statistically not significant (p = 0.405). Conclusions: The serum IgG4/IgG1 or IgG4/(IgG1+IgG3) level may help to differentiate IgG4-SC from PSC. IgG4 alone is the most accurate serologic marker for the differentiation of IgG4-SC from CCA.

Automated summary

This study aimed to find the best combinations of serum markers for differentiating IgG4-SC from PSC or CCA. The results showed that serum IgG4/IgG1 or IgG4/(IgG1+IgG3) levels can help differentiate IgG4-SC from PSC, while IgG4 alone is the most accurate marker for differentiating IgG4-SC from CCA.