Fucosylation of IgG heavy chains is increased in rheumatoid arthritis

Gornik, Ivan; Maravić, Gordana; Dumić, Jerka; Flögel, Mirna; Lauc, Gordan

doi:10.1016/s0009-9120(99)00060-0

Cited by 70 publications

(57 citation statements)

References 12 publications

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“…IgG galactosylation and fucosylation changes going in different directions have been previously described for juvenile chronic arthritis and rheumatoid arthritis. 32,33 For both sexes and both IgG1 Fc N-glycans and IgG2&3 Fc N-glycans, we confirmed an increasing incidence of bisecting GlcNAc with age. [17][18][19][20]23 In accordance with Yamada et al who have reported the level of bisecting GlcNAc reaching a plateau at the age of 50 years, 18 we did not detect a correlation between age and bisecting GlcNAc in older individuals.…”

Section: ■ Discussionsupporting

confidence: 58%

High-Throughput IgG Fc N-Glycosylation Profiling by Mass Spectrometry of Glycopeptides

et al. 2013

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Age and sex dependence of subclass specific immunoglobulin G (IgG) Fc N-glycosylation was evaluated for 1709 individuals from two isolated human populations. IgGs were obtained from plasma by affinity purification using 96-well protein G monolithic plates and digested with trypsin. Fc Nglycopeptides were purified and analyzed by negative-mode MALDI-TOF-MS with 4-chloro-α-cyanocinnamic acid (Cl-CCA) matrix. Age-associated glycosylation changes were more pronounced in younger individuals (<57 years) than in older individuals (>57 years) and in females than in males. Galactosylation and sialylation decreased with increasing age and showed significant sex dependence. Interestingly, the most prominent drop in the levels of galactosylated and sialylated glycoforms in females was observed around the age of 45 to 60 years when females usually enter menopause. The incidence of bisecting N-acetylglucosamine increased in younger individuals and reached a plateau at older age. Furthermore, we compared the results to the total IgG N-glycosylation of the same populations recently analyzed by hydrophilic interaction liquid chromatography (HILIC). Significant differences were observed in the levels of galactosylation, bisecting N-acetylglucosamine and particularly sialylation, which were shown to be higher in HILIC analysis. Age and sex association of glycosylation features was, to a large extent, comparable between MALDI-TOF-MS and HILIC IgG glycosylation profiling.

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Section: ■ Discussionsupporting

confidence: 58%

High-Throughput IgG Fc N-Glycosylation Profiling by Mass Spectrometry of Glycopeptides

et al. 2013

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“…37 The fucosylation of denatured IgG heavy chains was significantly increased in RA as measured by lectin binding. 38 Furthermore, there is a positive correlation between galactosylation and sialylation of IgG with the improvement of RA during pregnancies and post-partum flares. 39 Glycans are potential ligands for a plethora of lectin receptors found on immune effector cells, which are used as phagocytic receptors.…”

Section: Discussionmentioning

confidence: 99%

Altered glycosylation of complexed native IgG molecules is associated with disease activity of systemic lupus erythematosus

Sjöwall

Zapf

Löhneysen

et al. 2014

Lupus

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In addition to the redundancy of the receptors for the Fc portion of immunoglobulins, glycans result in potential ligands for a plethora of lectin receptors found in immune effector cells. Here we analysed the exposure of glycans containing fucosyl residues and the fucosylated tri-mannose N-type core by complexed native IgG in longitudinal serum samples of wellcharacterized patients with systemic lupus erythematosus. Consecutive serum samples of a cohort of 15 patients with systemic lupus erythematosus during periods of increased disease activity and remission were analysed. All patients fulfilled the 1982 American College of Rheumatology classification criteria. Sera of 15 sex-and age-matched normal healthy blood donors served as controls. The levels and type of glycosylation of complexed random IgG was measured with lectin enzyme-immunosorbent assays. After specifically gathering IgG complexes from sera, biotinylated lectins Aleuria aurantia lectin and Lens culinaris agglutinin were employed to detect IgG-associated fucosyl residues and the fucosylated tri-mannose N-glycan core, respectively. In sandwich-ELISAs, IgG-associated IgM, IgA, C1q, C3c and C-reactive protein (CRP) were detected as candidates for IgG immune complex constituents. We studied associations of the glycan of complexed IgG and disease activity according to the physician's global assessment of disease activity and the systemic lupus erythematosus disease activity index 2000 documented at the moment of blood taking. Our results showed significantly higher levels of Aleuria aurantia lectin and Lens culinaris agglutinin binding sites exposed on IgG complexes of patients with systemic lupus erythematosus than on those of normal healthy blood donors. Disease activity in systemic lupus erythematosus correlated with higher exposure of Aleuria aurantia lectin-reactive fucosyl residues by immobilized IgG complexes. Top levels of Aleuria aurantia lectin-reactivity were found in samples taken during the highest activity of systemic lupus erythematosus. Our results show that native circulating IgG complexes from active systemic lupus erythematosus patients expose fucosyl residues and their glycan core is accessible to soluble lectins. Two putative mechanisms may contribute to the increased exposure of these glycans: (1) the canonical N-glycosylation site of the IgG-CH2 domain; (2) an IgG binding non-IgG molecule, like complement or C-reactive protein. In both cases the complexed IgG may be alternatively targeted to lectin receptors of effector cells, e.g. dendritic cells. Lupus (2015) 24, 569-581.

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“…One particularly dramatic oligosaccharide change associated with disease is reduced galactose in IgG N-glycans seen in patients with rheumatoid arthritis (RA) [1]. Fucosylation of IgG [2] and N-glycan microheterogeneities in α1-acid glycoproteins (AGP) [3,4], transferrin [5], haptoglobin [6], α2-macrogloblin [7], and other plasma proteins [8] have also been reported in RA, although it is not known how alterations are associated with symptoms [9]. Several methods have been applied to the analysis of IgG N-glycans, such as reversed phase-high performance liquid chromatography (RP-HPLC), liquid chromatography-mass spectrometry (LC-MS), lectin analysis, and high pH anion exchange chromatography-pulsed amperometric detection (HPAEC-PAD) [10].…”

Section: Introductionmentioning

confidence: 99%

Detection of altered N-glycan profiles in whole serum from rheumatoid arthritis patients

Nakagawa

Hato

Takegawa

et al. 2007

Journal of Chromatography B

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Altered N-glycosylation occurs in many diseases. In rheumatoid arthritis (RA), for example, reduction in galactose residues in IgG and an increase in fucose residues in α1-acid glycoprotein have been observed. To further analysis of N-glycans in disease, we show N-glycan profiling from whole serum employing reversed phase high performance liquid chromatography/negative-ion mode by sonic spray ionization ion trap mass spectrometry with pyridylamination. Profiles from female 15 RA patients and 18 aged-matched healthy women were compared. The most significant change seen in RA was decreased levels of mono-galactosyl bi-antennary N-glycans, in agreement with previous reports regarding IgG.We also show previously unreported differences between isomers and increased tri-antennary oligosaccharides. These results indicate that LC-MS analysis of whole serum N-glycans can identify N-glycan alterations in RA and that this is a promising method both for studies of RA mechanisms and diagnosis.

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Fucosylation of IgG heavy chains is increased in rheumatoid arthritis

Cited by 70 publications

References 12 publications

High-Throughput IgG Fc N-Glycosylation Profiling by Mass Spectrometry of Glycopeptides

High-Throughput IgG Fc N-Glycosylation Profiling by Mass Spectrometry of Glycopeptides

Altered glycosylation of complexed native IgG molecules is associated with disease activity of systemic lupus erythematosus

Detection of altered N-glycan profiles in whole serum from rheumatoid arthritis patients

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