Unique patterns of glycosylation in immunoglobulin subclass G4‐related disease and primary sclerosing cholangitis
<p>Background: Immunoglobulin subclass G4‐related disease (IgG4‐RD) is characterized by an abundance of IgG4 antibodies in the serum and tissue. Glycosylation status of antibodies can impact on immune effector functions and disease pathophysiology. We sought to establish glycosylation patterns...
| Main Authors: | , , , , , , , , , , |
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| Format: | Journal article |
| Language: | English |
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Wiley
2018
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| _version_ | 1797063106364440576 |
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| author | Culver, E Van De Bovenkamp, F Derksen, N Koers, J Cargill, T Barnes, E De Neef, L Koeleman, C Aalberse, R Wuhrer, M Rispens, T |
| author_facet | Culver, E Van De Bovenkamp, F Derksen, N Koers, J Cargill, T Barnes, E De Neef, L Koeleman, C Aalberse, R Wuhrer, M Rispens, T |
| author_sort | Culver, E |
| collection | OXFORD |
| description | <p>Background: Immunoglobulin subclass G4‐related disease (IgG4‐RD) is characterized by an abundance of IgG4 antibodies in the serum and tissue. Glycosylation status of antibodies can impact on immune effector functions and disease pathophysiology. We sought to establish glycosylation patterns in a prospective cohort of patients with IgG4‐RD and the relationship with disease activity and response to treatment.</p><p> Methods: We assessed IgG Fc‐tail and Fab‐arm glycosylation status in patients with IgG4‐RD (n = 22), disease controls with primary sclerosing cholangitis (PSC) (n = 22), and healthy controls (n = 22). Serum IgG and subclasses were quantified using ELISA. Fc and Fab glycosylation were analyzed by mass spectrometry and lectin affinity chromatography, respectively. Disease activity, organ damage, and response to treatment were assessed using the IgG4 Responder Index.</p><p> Results: Immunoglobulin G Fab sialylation was increased in IgG4‐RD compared with PSC and healthy control (P = 0.01), with a preferential increase in IgG4‐specific Fab sialylation, which was independent of IgG4 Fab‐arm exchange. There was a reduction in IgG1‐specific Fc bisection and hybrid structures in IgG4‐RD (P < 0.01), which recovered upon steroid treatment and correlated with disease activity. Overall, IgG Fc galactosylation was reduced in both IgG4‐RD and PSC (P < 0.01), with a preferential reduction in IgG1‐specific sialylation and enhancement of IgG4‐specific bisection in PSC. IgG4 fucosylation and IgG1/2/3 hybrid structures negatively correlated with complement C3 and C4 levels in IgG4‐RD (P < 0.01), but not PSC.</p><p> Conclusion: We report the first study showing unique antibody glycosylation status in a prospective cohort of IgG4‐RD and PSC patients, which may determine modulation of the immune system and contribute to disease pathophysiology.</p> |
| first_indexed | 2024-03-06T20:55:05Z |
| format | Journal article |
| id | oxford-uuid:38efd191-6112-46f0-87ac-485e8824bdc6 |
| institution | University of Oxford |
| language | English |
| last_indexed | 2024-03-06T20:55:05Z |
| publishDate | 2018 |
| publisher | Wiley |
| record_format | dspace |
| spelling | oxford-uuid:38efd191-6112-46f0-87ac-485e8824bdc62022-03-26T13:52:50ZUnique patterns of glycosylation in immunoglobulin subclass G4‐related disease and primary sclerosing cholangitisJournal articlehttp://purl.org/coar/resource_type/c_dcae04bcuuid:38efd191-6112-46f0-87ac-485e8824bdc6EnglishSymplectic Elements at OxfordWiley2018Culver, EVan De Bovenkamp, FDerksen, NKoers, JCargill, TBarnes, EDe Neef, LKoeleman, CAalberse, RWuhrer, MRispens, T<p>Background: Immunoglobulin subclass G4‐related disease (IgG4‐RD) is characterized by an abundance of IgG4 antibodies in the serum and tissue. Glycosylation status of antibodies can impact on immune effector functions and disease pathophysiology. We sought to establish glycosylation patterns in a prospective cohort of patients with IgG4‐RD and the relationship with disease activity and response to treatment.</p><p> Methods: We assessed IgG Fc‐tail and Fab‐arm glycosylation status in patients with IgG4‐RD (n = 22), disease controls with primary sclerosing cholangitis (PSC) (n = 22), and healthy controls (n = 22). Serum IgG and subclasses were quantified using ELISA. Fc and Fab glycosylation were analyzed by mass spectrometry and lectin affinity chromatography, respectively. Disease activity, organ damage, and response to treatment were assessed using the IgG4 Responder Index.</p><p> Results: Immunoglobulin G Fab sialylation was increased in IgG4‐RD compared with PSC and healthy control (P = 0.01), with a preferential increase in IgG4‐specific Fab sialylation, which was independent of IgG4 Fab‐arm exchange. There was a reduction in IgG1‐specific Fc bisection and hybrid structures in IgG4‐RD (P < 0.01), which recovered upon steroid treatment and correlated with disease activity. Overall, IgG Fc galactosylation was reduced in both IgG4‐RD and PSC (P < 0.01), with a preferential reduction in IgG1‐specific sialylation and enhancement of IgG4‐specific bisection in PSC. IgG4 fucosylation and IgG1/2/3 hybrid structures negatively correlated with complement C3 and C4 levels in IgG4‐RD (P < 0.01), but not PSC.</p><p> Conclusion: We report the first study showing unique antibody glycosylation status in a prospective cohort of IgG4‐RD and PSC patients, which may determine modulation of the immune system and contribute to disease pathophysiology.</p> |
| spellingShingle | Culver, E Van De Bovenkamp, F Derksen, N Koers, J Cargill, T Barnes, E De Neef, L Koeleman, C Aalberse, R Wuhrer, M Rispens, T Unique patterns of glycosylation in immunoglobulin subclass G4‐related disease and primary sclerosing cholangitis |
| title | Unique patterns of glycosylation in immunoglobulin subclass G4‐related disease and primary sclerosing cholangitis |
| title_full | Unique patterns of glycosylation in immunoglobulin subclass G4‐related disease and primary sclerosing cholangitis |
| title_fullStr | Unique patterns of glycosylation in immunoglobulin subclass G4‐related disease and primary sclerosing cholangitis |
| title_full_unstemmed | Unique patterns of glycosylation in immunoglobulin subclass G4‐related disease and primary sclerosing cholangitis |
| title_short | Unique patterns of glycosylation in immunoglobulin subclass G4‐related disease and primary sclerosing cholangitis |
| title_sort | unique patterns of glycosylation in immunoglobulin subclass g4 related disease and primary sclerosing cholangitis |
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