title: Serum immunoglobulin G4 and immunoglobulin G1 for distinguishing immunoglobulin G4-associated cholangitis from primary sclerosing cholangitis.
abstract: 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).
  
  
  CONCLUSIONS
  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.
authors.affiliation: Department of Gastroenterology and Hepatology, Academic Medical Center, Amsterdam, the Netherlands.
authors.forename: Kirsten
authors.initials: K
authors.lastname: Boonstra
authors.forename: Emma L
authors.initials: EL
authors.lastname: Culver
authors.forename: Lucas Maillette
authors.initials: LM
authors.lastname: de Buy Wenniger
authors.forename: Marianne J
authors.initials: MJ
authors.lastname: van Heerde
authors.forename: Karel J
authors.initials: KJ
authors.lastname: van Erpecum
authors.forename: Alexander C
authors.initials: AC
authors.lastname: Poen
authors.forename: Karin M J
authors.initials: KM
authors.lastname: van Nieuwkerk
authors.forename: B W Marcel
authors.initials: BW
authors.lastname: Spanier
authors.forename: Ben J M
authors.initials: BJ
authors.lastname: Witteman
authors.forename: Hans A R E
authors.initials: HA
authors.lastname: Tuynman
authors.forename: Nan
authors.initials: N
authors.lastname: van Geloven
authors.forename: Henk
authors.initials: H
authors.lastname: van Buuren
authors.forename: Roger W
authors.initials: RW
authors.lastname: Chapman
authors.forename: Eleanor
authors.initials: E
authors.lastname: Barnes
authors.forename: Ulrich
authors.initials: U
authors.lastname: Beuers
authors.forename: Cyriel Y
authors.initials: CY
authors.lastname: Ponsioen
mesh_terms: D000328:Adult; D000368:Aged; D002761:Cholangitis / Q000175:diagnosis / Q000276:immunology*; D015209:Cholangitis, Sclerosing / Q000175:diagnosis / Q000276:immunology*; D005260:Female; D006801:Humans; D007074:Immunoglobulin G / Q000097:blood* / Q000145:classification; D008297:Male; D008875:Middle Aged; D011237:Predictive Value of Tests
chemical_list: D007074:Immunoglobulin G