IgG Oligosaccharide Alterations Are a Novel Diagnostic Marker for Disease Activity and the Clinical Course of Inflammatory Bowel Disease

Shinzaki, Shinichiro; Iijima, Hideki; Nakagawa, Takatoshi; Egawa, Satoshi; Nakajima, Sachiko; Ishii, Shuji; Irie, Takanobu; Kakiuchi, Yohei; Nishida, Tsutomu; Yasumaru, Masakazu; Kanto, Tatsuya; Tsujii, Masahiko; Tsuji, S.; Mizushima, Tsunekazu; Yoshihara, Hiroyuki; Kondo, Akihiro; Miyoshi, Eiji; Hayashi, Norio

doi:10.1111/j.1572-0241.2007.01699.x

Cited by 65 publications

(54 citation statements)

References 36 publications

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“…Most of them end with either two N-acetylglucosamines (i.e., agalactosylated G0 glycoform), one galactose and one N-acetylglucosamine (G1), or two galactose residues (G2), but a significant, although minor, fraction of galactosylated glycans bears one or two terminal sialic acids (S1 or S2). It has been shown that the proportion of IgG lacking galactose is significantly increased in patients with a variety of chronic inflammatory diseases, most notably rheumatoid arthritis (4,(6)(7)(8)(9)(10). Increased levels of agalactosylated IgG have been shown to correlate with disease severity and also have prognostic value.…”

mentioning

confidence: 99%

Lack of Galactosylation Enhances the Pathogenic Activity of IgG1 but Not IgG2a Anti-Erythrocyte Autoantibodies

Ito

Furukawa

Yamada

et al. 2014

The Journal of Immunology

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IgG bears asparagine-linked oligosaccharide side chains in the Fc region. Variations in their extent of galactosylation and sialylation could modulate IgG Fc-dependent effector functions, and hence Ab activity. However, it has not yet been clarified whether the pathogenic potential of IgG autoantibodies is consistently enhanced by the absence of galactose residues per se or the lack of terminal sialylation, which is dependent on galactosylation. Moreover, it remains to be defined whether the increased pathogenicity of agalactosylated IgG is related to activation of the complement pathway by mannose-binding lectin, as suggested by in vitro studies. Using a murine model of autoimmune hemolytic anemia, we defined the contribution of galactosylation or sialylation to the pathogenic activity of IgG1 and IgG2a anti-erythrocyte class-switch variants of 34-3C monoclonal autoantibody. We generated their degalactosylated or highly sialylated glycovariants and compared their pathogenic effects with those of highly galactosylated or desialylated counterparts. Our results demonstrated that lack of galactosylation, but not sialylation, enhanced the pathogenic activity of 34-3C IgG1, but not IgG2a autoantibodies. Moreover, analysis of in vivo complement activation and of the pathogenic activity in mice deficient in C3 or IgG FcRs excluded the implication of mannose-binding lectin-mediated complement activation in the enhanced pathogenic effect of agalactosylated IgG1 anti-erythrocyte autoantibodies.

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mentioning

confidence: 99%

Lack of Galactosylation Enhances the Pathogenic Activity of IgG1 but Not IgG2a Anti-Erythrocyte Autoantibodies

Ito

Furukawa

Yamada

et al. 2014

The Journal of Immunology

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“…Shinzaki et al 8,10 have demonstrated higher serum agalactosyl IgG in Japanese patients with IBD, and an association with disease prognosis and response to therapy in this population. Another Japanese group reported that glycosylation alterations on IgA antibodies in patients with CD also correlated with disease activity.…”

Section: Discussionmentioning

confidence: 89%

“…5,7 In Japanese patients with inflammatory bowel disease (IBD), the agalactosyl fraction of IgG oligosaccharides was reported to correlate with disease activity and clinical course. 8 Recent data from this group also suggested an association with response to anti-TNF therapy, but the rheumatology literature has not confirmed these findings. 9,10 …”

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confidence: 94%

Lectin-reactive Anti-α-Gal in Patients with Crohnʼs Disease

Safaie

Ham

Kuang

et al. 2013

Inflammatory Bowel Diseases

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Background Patients with inflammatory bowel disease have higher proportions of immunoglobulin G (IgG) antibodies lacking N-galactose, also called agalactosyl IgG, in their serum. Such agalactosyl IgGs have been associated with disease activity and the immunogenicity of biologics. The aim was to describe the relationship between circulating levels of a subset of agalactosyl IgGs (anti-α-Gal) and Crohn’s disease (CD) phenotypes. Methods Prospectively collected serum samples of a well-characterized cohort of patients with inflammatory bowel disease and controls were used. Serum anti-α-Gal levels were measured by a high-affinity enzyme-linked immunosorbent assay and referenced to a standard control. Results Serum samples from 167 subjects were tested; 62 with CD, 76 with ulcerative colitis, and 29 controls. Agalactosyl anti-α-Gal levels were significantly higher in active CD than in active ulcerative colitis (P = 0.0043) or healthy controls (P < 0.0001). Among patients with CD, agalactosyl anti-α-Gal levels were significantly higher in those with a history of arthritis, than those without (P = 0.0002), but lower in those taking immunomodulators (P = 0.03). There was no correlation between agalactosyl anti-α-Gal levels and indices of Crohn’s severity, including C-reactive protein levels or Harvey– Bradshaw index. Patients who were primary or secondary nonresponders to infliximab had similar agalactosyl anti-α-Gal levels to clinical responders. Conclusions Patients with CD have greater amounts of agalactosylated anti-α-Gal antibodies in their serum, particularly in those with associated joint disease. This increase seems to be independent of indices of disease activity, but is influenced by immunomodulator use.

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“…In 2008, Shinzaki et al [69] reported the diagnostic value of N-linked oligosaccharides of IgG structure (agalactosyl fraction of the fucosylated IgG oligosaccharides [G0F/G2F]) in IBD. Later, the same team reported oligosaccharide alterations of IgA as a novel IBD biomarker in a cohort of 32 CD patients, 30 UC patients, and 30 healthy controls [70].…”

Section: N-acetylgalactosamines Per Hinge Glycopeptidementioning

confidence: 99%

Molecular Analysis of Inflammatory Bowel Disease: Clinically Useful Tools for Diagnosis, Response Prediction, and Monitoring of Targeted Therapy

Jiang

2015

Mol Diagn Ther

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Biomarkers of inflammatory bowel disease (IBD) are non-invasive or minimally invasive tests for IBD diagnosis and/or prognosis as well as assessment of disease activity and response to therapy. Here, we update the current status of IBD biomarkers, including serological, fecal, and genetic (DNA and microRNA [miRNA]) biomarkers. As an update, the classical serological biomarkers, including ASCA, pANCA, anti-OmpC, anti-Cbir, anti-I2, and other anti-glycan antibodies, are discussed only briefly. Emphasis in this article is given to those that have been recently identified or extensively characterized, as well as to the clinical utilities of biomarkers, with special attention to prediction of disease complication and activity assessment, mucosal healing, and response to therapies. In particular, we discuss the utilities of blood-based biomarkers predicting therapeutic response to anti-tumor necrosis factor (TNF)-α, such as anti-anti-TNFα antibodies or anti-drug antibodies (ADA) and trough level of anti-TNFα. Fecal biomarkers, which have recently attracted substantial attention, are also discussed extensively, including the well-characterized calprotectin and lactoferrin, as well as the recently characterized M2-PK, CHI3L1, neopterin, MMP-9, and HMGB1. Genome and exome sequencing enables the discovery of a number of rare yet disease-defining IBD-susceptible genes, particularly those involved in very early onset IBD, providing rare yet extremely useful biomarkers at genetic levels for IBD diagnosis/prognosis. Finally, we briefly summarize the discovery, characterization, and potential implications of miRNA as potential IBD biomarkers.

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IgG Oligosaccharide Alterations Are a Novel Diagnostic Marker for Disease Activity and the Clinical Course of Inflammatory Bowel Disease

Abstract: G0F/G2F is a potentially effective diagnostic marker of disease activity in both CD and UC, and of the clinical course in UC. A pathophysiologic difference between CD and UC was also demonstrated.

Cited by 65 publications

References 36 publications

Lack of Galactosylation Enhances the Pathogenic Activity of IgG1 but Not IgG2a Anti-Erythrocyte Autoantibodies

Lack of Galactosylation Enhances the Pathogenic Activity of IgG1 but Not IgG2a Anti-Erythrocyte Autoantibodies

Lectin-reactive Anti-α-Gal in Patients with Crohnʼs Disease

Molecular Analysis of Inflammatory Bowel Disease: Clinically Useful Tools for Diagnosis, Response Prediction, and Monitoring of Targeted Therapy

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