Galactosylation and Sialylation Levels of IgG Predict Relapse in Patients With PR3-ANCA Associated Vasculitis
Objective: The objective of our study is to investigate the Fc glycosylation profiles of both antigen-specific IgG targeted against proteinase 3 (PR3-ANCA) and total IgG as prognostic markers of relapse in patients with Granulomatosis with Polyangiitis (GPA). Methods: Seventy-five patients with GPA...
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| Format: | Article |
| Language: | English |
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Elsevier
2017-03-01
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| Series: | EBioMedicine |
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| Online Access: | http://www.sciencedirect.com/science/article/pii/S2352396417300373 |
| _version_ | 1818129978391265280 |
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| author | Michael J. Kemna Rosina Plomp Pieter van Paassen Carolien A.M. Koeleman Bas C. Jansen Jan G.M.C. Damoiseaux Jan Willem Cohen Tervaert Manfred Wuhrer |
| author_facet | Michael J. Kemna Rosina Plomp Pieter van Paassen Carolien A.M. Koeleman Bas C. Jansen Jan G.M.C. Damoiseaux Jan Willem Cohen Tervaert Manfred Wuhrer |
| author_sort | Michael J. Kemna |
| collection | DOAJ |
| description | Objective: The objective of our study is to investigate the Fc glycosylation profiles of both antigen-specific IgG targeted against proteinase 3 (PR3-ANCA) and total IgG as prognostic markers of relapse in patients with Granulomatosis with Polyangiitis (GPA).
Methods: Seventy-five patients with GPA and a PR3-ANCA rise during follow-up were included, of whom 43 patients relapsed within a median period of 8 (2–16) months. The N-glycan at Asn297 of affinity-purified and denatured total IgG and PR3-ANCA was determined by mass spectrometry of glycopeptides in samples obtained at the time of the PR3-ANCA rise and at the time of the relapse or time-matched during remission.
Results: Patients with total IgG1 exhibiting low galactosylation or low sialylation were highly prone to relapse after an ANCA rise (HR 3.46 [95%-CI 1.73–6.96], p < 0.0001 and HR 3.22 [95%-CI 1.52–6.83], p = 0.002, respectively).
In relapsing patients, total IgG1 galactosylation, sialylation and bisection significantly decreased and fucosylation significantly increased from the time of the PR3-ANCA rise to the relapse (p < 0.0001, p = 0.0087, p < 0.0001 and p = 0.0025), while the glycosylation profile remained similar in non-relapsing patients. PR3-ANCA IgG1 galactosylation, sialylation and fucosylation of PR3-ANCA IgG1 decreased in relapsing patients (p = 0.0073, p = 0.0049 and p = 0.0205), but also in non-relapsing patients (p = 0.0007, p = 0.0114 and p = 0.0002), while bisection increased only in non-relapsing patients (p < 0.0001).
Conclusion: While Fc glycosylation profiles have been associated with clinically manifest autoimmune diseases, in the present study we show that low galactosylation and sialyation in total IgG1 but not PR3-ANCA IgG1 predicts disease reactivation in patients with GPA who experience an ANCA rise during follow-up. We postulate that glycosylation profiles may be useful in pre-emptive therapy studies using ANCA rises as guideline. |
| first_indexed | 2024-12-11T07:57:44Z |
| format | Article |
| id | doaj.art-bbe80d4a90ea4097a03cd23d9193992b |
| institution | Directory Open Access Journal |
| issn | 2352-3964 |
| language | English |
| last_indexed | 2024-12-11T07:57:44Z |
| publishDate | 2017-03-01 |
| publisher | Elsevier |
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| series | EBioMedicine |
| spelling | doaj.art-bbe80d4a90ea4097a03cd23d9193992b2022-12-22T01:15:12ZengElsevierEBioMedicine2352-39642017-03-0117C10811810.1016/j.ebiom.2017.01.033Galactosylation and Sialylation Levels of IgG Predict Relapse in Patients With PR3-ANCA Associated VasculitisMichael J. Kemna0Rosina Plomp1Pieter van Paassen2Carolien A.M. Koeleman3Bas C. Jansen4Jan G.M.C. Damoiseaux5Jan Willem Cohen Tervaert6Manfred Wuhrer7Cardiovascular Research Institute Maastricht (CARIM), Maastricht University, Maastricht, The NetherlandsCentral Diagnostic Laboratory, Maastricht University Medical Center, Maastricht, The NetherlandsCardiovascular Research Institute Maastricht (CARIM), Maastricht University, Maastricht, The NetherlandsCenter for Proteomics and Metabolomics, Leiden University Medical Center, Leiden, The NetherlandsCenter for Proteomics and Metabolomics, Leiden University Medical Center, Leiden, The NetherlandsCentral Diagnostic Laboratory, Maastricht University Medical Center, Maastricht, The NetherlandsCardiovascular Research Institute Maastricht (CARIM), Maastricht University, Maastricht, The NetherlandsCenter for Proteomics and Metabolomics, Leiden University Medical Center, Leiden, The NetherlandsObjective: The objective of our study is to investigate the Fc glycosylation profiles of both antigen-specific IgG targeted against proteinase 3 (PR3-ANCA) and total IgG as prognostic markers of relapse in patients with Granulomatosis with Polyangiitis (GPA). Methods: Seventy-five patients with GPA and a PR3-ANCA rise during follow-up were included, of whom 43 patients relapsed within a median period of 8 (2–16) months. The N-glycan at Asn297 of affinity-purified and denatured total IgG and PR3-ANCA was determined by mass spectrometry of glycopeptides in samples obtained at the time of the PR3-ANCA rise and at the time of the relapse or time-matched during remission. Results: Patients with total IgG1 exhibiting low galactosylation or low sialylation were highly prone to relapse after an ANCA rise (HR 3.46 [95%-CI 1.73–6.96], p < 0.0001 and HR 3.22 [95%-CI 1.52–6.83], p = 0.002, respectively). In relapsing patients, total IgG1 galactosylation, sialylation and bisection significantly decreased and fucosylation significantly increased from the time of the PR3-ANCA rise to the relapse (p < 0.0001, p = 0.0087, p < 0.0001 and p = 0.0025), while the glycosylation profile remained similar in non-relapsing patients. PR3-ANCA IgG1 galactosylation, sialylation and fucosylation of PR3-ANCA IgG1 decreased in relapsing patients (p = 0.0073, p = 0.0049 and p = 0.0205), but also in non-relapsing patients (p = 0.0007, p = 0.0114 and p = 0.0002), while bisection increased only in non-relapsing patients (p < 0.0001). Conclusion: While Fc glycosylation profiles have been associated with clinically manifest autoimmune diseases, in the present study we show that low galactosylation and sialyation in total IgG1 but not PR3-ANCA IgG1 predicts disease reactivation in patients with GPA who experience an ANCA rise during follow-up. We postulate that glycosylation profiles may be useful in pre-emptive therapy studies using ANCA rises as guideline.http://www.sciencedirect.com/science/article/pii/S2352396417300373PR3-ANCA associated vasculitisGranulomatosis with PolyangiitisGlycosylationGlycopeptideImmunoglobulinMass spectrometry |
| spellingShingle | Michael J. Kemna Rosina Plomp Pieter van Paassen Carolien A.M. Koeleman Bas C. Jansen Jan G.M.C. Damoiseaux Jan Willem Cohen Tervaert Manfred Wuhrer Galactosylation and Sialylation Levels of IgG Predict Relapse in Patients With PR3-ANCA Associated Vasculitis EBioMedicine PR3-ANCA associated vasculitis Granulomatosis with Polyangiitis Glycosylation Glycopeptide Immunoglobulin Mass spectrometry |
| title | Galactosylation and Sialylation Levels of IgG Predict Relapse in Patients With PR3-ANCA Associated Vasculitis |
| title_full | Galactosylation and Sialylation Levels of IgG Predict Relapse in Patients With PR3-ANCA Associated Vasculitis |
| title_fullStr | Galactosylation and Sialylation Levels of IgG Predict Relapse in Patients With PR3-ANCA Associated Vasculitis |
| title_full_unstemmed | Galactosylation and Sialylation Levels of IgG Predict Relapse in Patients With PR3-ANCA Associated Vasculitis |
| title_short | Galactosylation and Sialylation Levels of IgG Predict Relapse in Patients With PR3-ANCA Associated Vasculitis |
| title_sort | galactosylation and sialylation levels of igg predict relapse in patients with pr3 anca associated vasculitis |
| topic | PR3-ANCA associated vasculitis Granulomatosis with Polyangiitis Glycosylation Glycopeptide Immunoglobulin Mass spectrometry |
| url | http://www.sciencedirect.com/science/article/pii/S2352396417300373 |
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