These authors contributed equally to the study.
Autoimmune, Cholestatic and Biliary Disease
Serum immunoglobulin G4 and immunoglobulin G1 for distinguishing immunoglobulin G4-associated cholangitis from primary sclerosing cholangitis
Article first published online: 1 APR 2014
© 2014 The Authors. Hepatology published by Wiley Periodicals, Inc., on behalf of American Association for the Study of Liver Diseases.
This is an open access article under the terms of the Creative Commons Attribution License, which permits use, distribution and reproduction in any medium, provided the original work is properly cited.
Volume 59, Issue 5, pages 1954–1963, May 2014
How to Cite
Boonstra, K., Culver, E. L., de Buy Wenniger, L. M., van Heerde, M. J., van Erpecum, K. J., Poen, A. C., van Nieuwkerk, K. M.J., Spanier, B.W. M., Witteman, B. J.M., Tuynman, H. A.R.E., van Geloven, N., van Buuren, H., Chapman, R. W., Barnes, E., Beuers, U. and Ponsioen, C. Y. (2014), Serum immunoglobulin G4 and immunoglobulin G1 for distinguishing immunoglobulin G4-associated cholangitis from primary sclerosing cholangitis. Hepatology, 59: 1954–1963. doi: 10.1002/hep.26977
Potential conflict of interest: Dr. Ponsioen received grants from Tramedico, Dr. Falk, and Zambon.
This research was supported by a Ph.D. fellowship of the Academic Medical Center Amsterdam (to L.M.W.), a Wellcome Trust Fellowship grant (095160/Z/10/Z; to E.C.), a Senior Clinician Scientist funding by the Medical Research Council, UK (to E.B.), grants “Primary sclerosing cholangitis” by the Deutsche Crohn und Colitis Vereinigung (DCCV) and the Norwegian Primary Sclerosing Cholangitis (NoPSC) Foundation (to U.B.), and unrestricted grants from AbbVie Inc., the Netherlands, Tramedico Inc., the Netherlands, Dr. Falk Pharma Benelux Inc., and Zambon Inc., the Netherlands (to C.P.).
The copyright line in this article was changed on 5 February 2015 after original online publication.
- Issue published online: 23 APR 2014
- Article first published online: 1 APR 2014
- Accepted manuscript online: 21 DEC 2013 12:25AM EST
- Manuscript Accepted: 17 DEC 2013
- Manuscript Received: 20 MAY 2013
The recent addition of immunoglobulin (Ig)G4-associated cholangitis (IAC), also called IgG4-related sclerosing cholangitis (IRSC), to the spectrum of chronic cholangiopathies has created the clinical need for reliable methods to discriminate between IAC and the more common cholestatic entities, primary (PSC) and secondary sclerosing cholangitis. The current American Association for the Study of Liver Diseases practice guidelines for PSC advise on the measurement of specific Ig (sIg)G4 in PSC patients, but interpretation of elevated sIgG4 levels remains unclear. We aimed to provide an algorithm to distinguish IAC from PSC using sIgG analyses. We measured total IgG and IgG subclasses in serum samples of IAC (n = 73) and PSC (n = 310) patients, as well as in serum samples of disease controls (primary biliary cirrhosis; n = 22). sIgG4 levels were elevated above the upper limit of normal (ULN = >1.4 g/L) in 45 PSC patients (15%; 95% confidence interval [CI]: 11-19). The highest specificity and positive predictive value (PPV; 100%) for IAC were reached when applying the 4× ULN (sIgG4 > 5.6 g/L) cutoff with a sensitivity of 42% (95% CI: 31-55). However, in patients with a sIgG4 between 1× and 2× ULN (n = 38/45), the PPV of sIgG4 for IAC was only 28%. In this subgroup, the sIgG4/sIgG1 ratio cutoff of 0.24 yielded a sensitivity of 80% (95% CI: 51-95), a specificity of 74% (95% CI: 57-86), a PPV of 55% (95% CI: 33-75), and a negative predictive value of 90% (95% CI: 73-97). Conclusion: Elevated sIgG4 (>1.4 g/L) occurred in 15% of patients with PSC. In patients with a sIgG4 >1.4 and <2.8 g/L, incorporating the IgG4/IgG1 ratio with a cutoff at 0.24 in the diagnostic algorithm significantly improved PPV and specificity. We propose a new diagnostic algorithm based on IgG4/IgG1 ratio that may be used in clinical practice to distinguish PSC from IAC. (Hepatology 2014;59:1954–1963)