Abstract
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-upwere 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 studywe 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. (C) 2017 The Authors. Published by Elsevier B.V.
Original language | English |
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Pages (from-to) | 108-118 |
Number of pages | 11 |
Journal | EBioMedicine |
Volume | 17 |
DOIs | |
Publication status | Published - Mar 2017 |
Keywords
- PR3-ANCA associated vasculitis
- Granulomatosis with Polyangiitis
- Glycosylation
- Glycopeptide
- Immunoglobulin
- Mass spectrometry
- ANCA-ASSOCIATED VASCULITIS
- ANTIBODY-ASSOCIATED VASCULITIS
- IMMUNOGLOBULIN-G
- RHEUMATOID-ARTHRITIS
- WEGENERS-GRANULOMATOSIS
- MEDIATED GLOMERULONEPHRITIS
- ANTIINFLAMMATORY ACTIVITY
- GLYCOSYLATION CHANGES
- SYSTEMIC VASCULITIS
- MASS-SPECTROMETRY