Galactosylation and Sialylation Levels of IgG Predict Relapse in Patients With PR3-ANCA Associated Vasculitis

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

*Corresponding author for this work

Research output: Contribution to journalArticleAcademicpeer-review

56 Citations (Web of Science)

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 languageEnglish
Pages (from-to)108-118
Number of pages11
JournalEBioMedicine
Volume17
DOIs
Publication statusPublished - 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

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