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


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-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.

SUBMITTER: Kemna MJ 

PROVIDER: S-EPMC5360573 | biostudies-literature | 2017 Mar

REPOSITORIES: biostudies-literature

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

Kemna Michael J MJ   Plomp Rosina R   van Paassen Pieter P   Koeleman Carolien A M CAM   Jansen Bas C BC   Damoiseaux Jan G M C JGMC   Cohen Tervaert Jan Willem JW   Wuhrer Manfred M  

EBioMedicine 20170128


<h4>Objective</h4>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).<h4>Methods</h4>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  ...[more]

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