Serum immunoglobulin G4 and immunoglobulin G1 for distinguishing immunoglobulin G4-associated cholangitis from primary sclerosing cholangitis.
UNLABELLED: 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 en...
| Main Authors: | , , , , , , , , , , , , , , , |
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| Format: | Journal article |
| Language: | English |
| Published: |
John Wiley and Sons Ltd
2014
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| _version_ | 1826268987009269760 |
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| author | Boonstra, K Culver, E de Buy Wenniger, L van Heerde, M van Erpecum, K Poen, A van Nieuwkerk, K Spanier, B Witteman, B Tuynman, H van Geloven, N van Buuren, H Chapman, R Barnes, E Beuers, U Ponsioen, C |
| author_facet | Boonstra, K Culver, E de Buy Wenniger, L van Heerde, M van Erpecum, K Poen, A van Nieuwkerk, K Spanier, B Witteman, B Tuynman, H van Geloven, N van Buuren, H Chapman, R Barnes, E Beuers, U Ponsioen, C |
| author_sort | Boonstra, K |
| collection | OXFORD |
| description | UNLABELLED: 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. |
| first_indexed | 2024-03-06T21:17:58Z |
| format | Journal article |
| id | oxford-uuid:407258a1-e0e4-4cf1-a1a5-da8ad80db5b9 |
| institution | University of Oxford |
| language | English |
| last_indexed | 2024-03-06T21:17:58Z |
| publishDate | 2014 |
| publisher | John Wiley and Sons Ltd |
| record_format | dspace |
| spelling | oxford-uuid:407258a1-e0e4-4cf1-a1a5-da8ad80db5b92022-03-26T14:38:02ZSerum immunoglobulin G4 and immunoglobulin G1 for distinguishing immunoglobulin G4-associated cholangitis from primary sclerosing cholangitis.Journal articlehttp://purl.org/coar/resource_type/c_dcae04bcuuid:407258a1-e0e4-4cf1-a1a5-da8ad80db5b9EnglishSymplectic Elements at OxfordJohn Wiley and Sons Ltd2014Boonstra, KCulver, Ede Buy Wenniger, Lvan Heerde, Mvan Erpecum, KPoen, Avan Nieuwkerk, KSpanier, BWitteman, BTuynman, Hvan Geloven, Nvan Buuren, HChapman, RBarnes, EBeuers, UPonsioen, CUNLABELLED: 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. |
| spellingShingle | Boonstra, K Culver, E de Buy Wenniger, L van Heerde, M van Erpecum, K Poen, A van Nieuwkerk, K Spanier, B Witteman, B Tuynman, H van Geloven, N van Buuren, H Chapman, R Barnes, E Beuers, U Ponsioen, C Serum immunoglobulin G4 and immunoglobulin G1 for distinguishing immunoglobulin G4-associated cholangitis from primary sclerosing cholangitis. |
| title | Serum immunoglobulin G4 and immunoglobulin G1 for distinguishing immunoglobulin G4-associated cholangitis from primary sclerosing cholangitis. |
| title_full | Serum immunoglobulin G4 and immunoglobulin G1 for distinguishing immunoglobulin G4-associated cholangitis from primary sclerosing cholangitis. |
| title_fullStr | Serum immunoglobulin G4 and immunoglobulin G1 for distinguishing immunoglobulin G4-associated cholangitis from primary sclerosing cholangitis. |
| title_full_unstemmed | Serum immunoglobulin G4 and immunoglobulin G1 for distinguishing immunoglobulin G4-associated cholangitis from primary sclerosing cholangitis. |
| title_short | Serum immunoglobulin G4 and immunoglobulin G1 for distinguishing immunoglobulin G4-associated cholangitis from primary sclerosing cholangitis. |
| title_sort | serum immunoglobulin g4 and immunoglobulin g1 for distinguishing immunoglobulin g4 associated cholangitis from primary sclerosing cholangitis |
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