Glycosylation as a marker for inflammatory arthritis

Albrecht, Simone; Unwin, Louise; Muniyappa, Mohankumar; Rudd, Pauline M.

doi:10.3233/cbm-130373

Cited by 65 publications

(45 citation statements)

References 121 publications

(167 reference statements)

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“…While IgG with a low degree of galactosylation has repeatedly been found to be associated with pro-inflammatory autoimmune responses, the underlying mechanisms are still largely elusive (Bondt et al, 2013, Matsumoto et al, 2000, Albrecht et al, 2014, Rademacher et al, 1994). In addition, highly galactosylated IgG may confer anti-inflammatory activities through the association with the inhibiting receptor FcyRIIb and the C-type lectin-like receptor Dectin-1 in mice (Karsten et al, 2012).…”

Section: Discussionmentioning

confidence: 99%

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

et al. 2017

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ObjectiveThe 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).MethodsSeventy-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.ResultsPatients 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).ConclusionWhile 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.

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Section: Discussionmentioning

confidence: 99%

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

et al. 2017

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“…The extent and nature of IgG Fc glycosylation vary with age , following immunization , and in some autoimmune diseases ; data indicate abnormalities in the IgG glycome in patients with SLE, with a reduction in galactosylation and sialylation of IgG that might potentially favor binding to classical activating FcγR . A reduction in galactosylation has also been observed in patients with rheumatoid arthritis , and changes in glycosylation of anti‐citrullinated protein autoantibodies predate disease progression . The pathophysiological relevance of these observations remains to be fully elucidated, but a recent study showed that desialylated immune complexes increase osteoclastogenesis in vitro and in vivo , and that mice treated with a sialic acid precursor to increase IgG sialylation were less susceptible to inflammatory bone loss due to altered FcγR binding .…”

Section: Fcγrs and Autoantibodies In Autoimmunitymentioning

confidence: 99%

FcγRIIB and autoimmunity

Espéli

Smith

Clatworthy

2015

Immunological Reviews

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Autoimmune diseases are characterized by adaptive immune responses against self-antigens, including humoral responses resulting in the production of autoantibodies. Autoantibodies generate inflammation by activating complement and engaging Fcγ receptors (FcγRs). The inhibitory receptor FcγRIIB plays a central role in regulating the generation of autoantibodies and their effector functions, which include activation of innate immune cells and the cellular arm of the adaptive immune system, via effects on antigen presentation to CD4 T cells. Polymorphisms in FcγRIIB have been associated with susceptibility to autoimmunity but protection against infections in humans and mice. In the last few years, new mechanisms by which FcγRIIB controls the adaptive immune response have been described. Notably, FcγRIIB has been shown to regulate germinal center B cells and dendritic cell migration, with potential impact on the development of autoimmune diseases. Recent work has also highlighted the implication of FcγRIIB on the regulation of the innate immune system, via inhibition of Toll-like receptor- and complement receptor-mediated activation. This review will provide an update on the role of FcγRIIB in adaptive immune responses in autoimmunity, and then focus on their emerging function in innate immunity.

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“…Changes in glycosylation may be associated with various factors, including age and pathophysiological conditions 4–7 . In certain disease settings, specific glycan features such as fucosylation, bisection, galactosylation or sialylation are known to be affected 8, 9 .…”

Section: Introductionmentioning

confidence: 99%

Sialic acid linkage differentiation of glycopeptides using capillary electrophoresis – electrospray ionization – mass spectrometry

Kammeijer

Jansen

Köhler

et al. 2017

Sci Rep

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Sialylation is a glycosylation feature that occurs in different linkages at the non-reducing end of a glycan moiety, the linkage isomers are often differentially associated with various biological processes. Due to very similar physico-chemical properties, the separation of isomeric sialylated glycopeptides remains challenging but of utmost importance in the biomedicine and biotechnology, including biomarker discovery, glyco-engineering and biopharmaceutical characterization. This study presents the implementation of a high-resolution separation platform based on capillary electrophoresis – mass spectrometry (CE–MS) allowing for the selective analysis of α2,3- and α2,6-sialylated glycopeptides. These differentially linked glycopeptides showed an identical fragmentation pattern (collision induced dissociation) but different electrophoretic mobilities, allowing for baseline separation of the different linkages without the need for an extensive sample preparation. The different migration behavior between the two moieties was found to correlate with differences in pKa values. Using a novel methodology adapted from the so-called internal standard CE approach, a relative difference of 3.4·10−2 in pKa unit was determined. This approach was applied for the analysis of tryptic glycopeptides of prostate specific antigen, which shows highly complex and heterogeneous glycosylation. The developed platform therefore appears attractive for the identification of differentially linked sialic acids that may be related to pathological conditions.

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Glycosylation as a marker for inflammatory arthritis

Cited by 65 publications

References 121 publications

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

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

FcγRIIB and autoimmunity

Sialic acid linkage differentiation of glycopeptides using capillary electrophoresis – electrospray ionization – mass spectrometry

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