A novel serum metabolomic panel distinguishes IgG4-related sclerosing cholangitis from primary sclerosing cholangitis
<p><strong>Background & Aims: </strong>Primary sclerosing cholangitis (PSC) and IgG4-related sclerosing cholangitis (IgG4-SC) are chronic fibro-inflammatory immune-mediated hepatobiliary conditions that are challenging to distinguish in a clinical setting. Accurate...
| المؤلفون الرئيسيون: | , , , , , , , , , , , |
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| التنسيق: | Journal article |
| اللغة: | English |
| منشور في: |
Wiley
2022
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| _version_ | 1826309558729965568 |
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| author | Radford-Smith, DE Selvaraj, EA Peters, R Orrell, M Bolon, J Anthony, DC Pavlides, M Lynch, K Geremia, A Bailey, A Culver, EL Probert, F |
| author_facet | Radford-Smith, DE Selvaraj, EA Peters, R Orrell, M Bolon, J Anthony, DC Pavlides, M Lynch, K Geremia, A Bailey, A Culver, EL Probert, F |
| author_sort | Radford-Smith, DE |
| collection | OXFORD |
| description | <p><strong>Background & Aims: </strong>Primary sclerosing cholangitis (PSC) and IgG4-related sclerosing cholangitis (IgG4-SC) are chronic fibro-inflammatory immune-mediated hepatobiliary conditions that are challenging to distinguish in a clinical setting. Accurate non-invasive biomarkers for discriminating PSC and IgG4-SC are important to ensure a correct diagnosis, prompt therapy and adequate cancer surveillance.</p>
<p><strong>Methods: </strong>We performed nuclear magnetic resonance (NMR)-based metabolomic profiling using serum samples collected prospectively from patients with PSC (<em>n</em> = 100), IgG4-SC (<em>n</em> = 23) and healthy controls (HC; <em>n</em> = 16).</p>
<p><strong>Results: </strong>Multivariate analysis of the serum metabolome discriminated PSC from IgG4-SC with greater accuracy (AUC 0.95 [95%CI 0.90–0.98]) than IgG4 titre (AUC 0.87 [95%CI 0.79–0.94]). When inflammatory bowel disease (IBD) was excluded as a comorbid condition (IgG4-SC <em>n</em> = 20, PSC <em>n</em> = 22), the diagnostic AUC increased to 1.0, suggesting that the metabolome differences identified are not a result of the increased prevalence of IBD in PSC relative to IgG4-SC patients. Serum lactate (<em>p</em> < .0001), glucose (<em>p</em> < .01) and glutamine (<em>p</em> < .01) metabolites were increased in IgG4-related disease (IgG4-RD) and IgG4-SC individuals compared to PSC, whereas mobile choline (<em>p</em> < .05), 3-hydroxybutyric acid (<em>p</em> < .01) and -CH<sub>3</sub> lipoprotein resonances (<em>p</em> < .01) were decreased.</p>
<p><strong>Conclusions: </strong>Taken together, serum metabolomic profiling has the potential to be incorporated as a diagnostic criterion, independent of IgG4 titre, to improve the diagnosis of IgG4-RD and help distinguish IgG4-SC from PSC.</p> |
| first_indexed | 2024-03-07T07:37:33Z |
| format | Journal article |
| id | oxford-uuid:272363cf-8200-44a2-9bb7-87faa4c7b29c |
| institution | University of Oxford |
| language | English |
| last_indexed | 2024-03-07T07:37:33Z |
| publishDate | 2022 |
| publisher | Wiley |
| record_format | dspace |
| spelling | oxford-uuid:272363cf-8200-44a2-9bb7-87faa4c7b29c2023-03-31T06:38:52ZA novel serum metabolomic panel distinguishes IgG4-related sclerosing cholangitis from primary sclerosing cholangitisJournal articlehttp://purl.org/coar/resource_type/c_dcae04bcuuid:272363cf-8200-44a2-9bb7-87faa4c7b29cEnglishSymplectic ElementsWiley2022Radford-Smith, DESelvaraj, EAPeters, ROrrell, MBolon, JAnthony, DCPavlides, MLynch, KGeremia, ABailey, ACulver, ELProbert, F<p><strong>Background & Aims: </strong>Primary sclerosing cholangitis (PSC) and IgG4-related sclerosing cholangitis (IgG4-SC) are chronic fibro-inflammatory immune-mediated hepatobiliary conditions that are challenging to distinguish in a clinical setting. Accurate non-invasive biomarkers for discriminating PSC and IgG4-SC are important to ensure a correct diagnosis, prompt therapy and adequate cancer surveillance.</p> <p><strong>Methods: </strong>We performed nuclear magnetic resonance (NMR)-based metabolomic profiling using serum samples collected prospectively from patients with PSC (<em>n</em> = 100), IgG4-SC (<em>n</em> = 23) and healthy controls (HC; <em>n</em> = 16).</p> <p><strong>Results: </strong>Multivariate analysis of the serum metabolome discriminated PSC from IgG4-SC with greater accuracy (AUC 0.95 [95%CI 0.90–0.98]) than IgG4 titre (AUC 0.87 [95%CI 0.79–0.94]). When inflammatory bowel disease (IBD) was excluded as a comorbid condition (IgG4-SC <em>n</em> = 20, PSC <em>n</em> = 22), the diagnostic AUC increased to 1.0, suggesting that the metabolome differences identified are not a result of the increased prevalence of IBD in PSC relative to IgG4-SC patients. Serum lactate (<em>p</em> < .0001), glucose (<em>p</em> < .01) and glutamine (<em>p</em> < .01) metabolites were increased in IgG4-related disease (IgG4-RD) and IgG4-SC individuals compared to PSC, whereas mobile choline (<em>p</em> < .05), 3-hydroxybutyric acid (<em>p</em> < .01) and -CH<sub>3</sub> lipoprotein resonances (<em>p</em> < .01) were decreased.</p> <p><strong>Conclusions: </strong>Taken together, serum metabolomic profiling has the potential to be incorporated as a diagnostic criterion, independent of IgG4 titre, to improve the diagnosis of IgG4-RD and help distinguish IgG4-SC from PSC.</p> |
| spellingShingle | Radford-Smith, DE Selvaraj, EA Peters, R Orrell, M Bolon, J Anthony, DC Pavlides, M Lynch, K Geremia, A Bailey, A Culver, EL Probert, F A novel serum metabolomic panel distinguishes IgG4-related sclerosing cholangitis from primary sclerosing cholangitis |
| title | A novel serum metabolomic panel distinguishes IgG4-related sclerosing cholangitis from primary sclerosing cholangitis |
| title_full | A novel serum metabolomic panel distinguishes IgG4-related sclerosing cholangitis from primary sclerosing cholangitis |
| title_fullStr | A novel serum metabolomic panel distinguishes IgG4-related sclerosing cholangitis from primary sclerosing cholangitis |
| title_full_unstemmed | A novel serum metabolomic panel distinguishes IgG4-related sclerosing cholangitis from primary sclerosing cholangitis |
| title_short | A novel serum metabolomic panel distinguishes IgG4-related sclerosing cholangitis from primary sclerosing cholangitis |
| title_sort | novel serum metabolomic panel distinguishes igg4 related sclerosing cholangitis from primary sclerosing cholangitis |
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