Sugar printing rheumatic diseases: A potential method for disease differentiation using immunoglobulin G oligosaccharides

Watson, Mando; Rudd, Pauline M.; Bland, Martin; Dwek, Raymond A.; Axford, John S.

doi:10.1002/1529-0131(199908)42:8<1682::aid-anr17>3.0.co;2-x

Cited by 74 publications

(52 citation statements)

References 33 publications

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“…This specific change in the glycosylation of immunoglobulins has been previously reported with various autoimmune diseases, such as rheumatoid arthritis and systemic lupus (26)(27)(28)36), and recently with bacterial infection and chronic infection with human immunodeficiency virus (23). Our work is the first report that identifies a specific immunoglobulin with this modification.…”

supporting

confidence: 80%

“…Additionally, such a simple assay would potentially have great benefit in the developing world. Although larger, more diverse studies are needed and a direct comparison to other noninvasive tests for cirrhosis is required (5,(35)(36)(37), this work lays the groundwork by suggesting that the determination of the amount of lectinreactive anti-Gal IgG will have value in the management of people with liver disease. In addition, the finding that alphaGal antibodies have increased reactivity to fucose binding lectins will allow the development of lectin FLISA-based methods for the analysis of glycoproteins that become hyperfucosylated with the development of HCC.…”

Section: Discussionmentioning

confidence: 95%

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Increased Levels of Galactose-Deficient Anti-Gal Immunoglobulin G in the Sera of Hepatitis C Virus-Infected Individuals with Fibrosis and Cirrhosis

Mehta

Long

Comunale

et al. 2008

J Virol

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114

119

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Hepatitis B and C viruses are major causative agents of liver fibrosis, cirrhosis, and liver cancer. Using comparative glycoproteomics, we identified a glycoprotein that is altered both in amount and in glycosylation as a function of liver fibrosis and cirrhosis. Specifically, this altered glycoprotein is an immunoglobulin G (IgG) molecule reactive to the heterophilic alpha-Gal epitope [Gal␣-1-3Gal␤1-(3)4GlcNAc-R]. While similar changes in glycosylation have been observed in several autoimmune diseases, the specific immunoglobulins and their antigen recognition profiles were not determined. Thus, we provide the first report identifying the specific antigenic recognition profile of an immunoglobulin molecule containing altered glycosylation as a function of liver disease. This change in glycosylation allowed increased reactivity with several fucose binding lectins and permitted the development of a plate-based assay to measure this change. Increased lectin reactivity was observed in 100% of the more than 200 individuals with stage III or greater fibrosis and appeared to be correlated with the degree of fibrosis. The reason for the alteration in the glycosylation of anti-Gal IgG is currently unclear but may be related to the natural history of the disease and may be useful in the noninvasive detection of fibrosis and cirrhosis.

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supporting

confidence: 80%

Section: Discussionmentioning

confidence: 95%

Increased Levels of Galactose-Deficient Anti-Gal Immunoglobulin G in the Sera of Hepatitis C Virus-Infected Individuals with Fibrosis and Cirrhosis

Mehta

Long

Comunale

et al. 2008

J Virol

Self Cite

114

119

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“…Changes in IgG glycan profiles are useful for early stage diagnosis of RA [25]. This method does not require IgG purification and can provide information about other serum proteins.…”

Section: Discussionmentioning

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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“…40,[82][83][84][85] Glycans as markers for diagnosis of specific autoimmune inflammatory diseases based on the glycosylation pattern of IgG have been reported. 84,86 Diseases caused by inherited or acquired glycoprotein oligosaccharide structural alterations have also been described. 85 The list of diseases caused by abnormal protein glycosylation is growing steadily, which may provide insight into their etiologies.…”

Section: Discussionmentioning

confidence: 99%

Sugar profiling proves that human serum erythropoietin differs from recombinant human erythropoietin

Skibeli

Nissen-Lie

Torjesen

2001

Blood

201

160

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Erythropoietin (EPO) from sera obtained from anemic patients was successfully isolated using magnetic beads coated with a human EPO (hEPO)-specific antibody. Human serum EPO emerged as a broad band after sodium dodecyl sulfatepolyacrylamide gel electrophoresis, with an apparent molecular weight slightly smaller than that of recombinant hEPO (rhEPO). The bandwidth corresponded with microheterogeneity because of extensive glycosylation. Two-dimensional gel electrophoresis revealing several different glycoforms confirmed the heterogeneity of circulating hEPO. The immobilized anti-hEPO antibody was capable of binding a representative selection of rhEPO glycoforms. This was shown by comparing normal-phase high-performance liquid chromatography profiles of oligosaccharides released from rhEPO with oligosaccharides released from rhEPO after isolation with hEPO-specific magnetic beads. Charge analysis demonstrated that human serum EPO contained only mono-, di-, and tri-acidic oligosaccharides and lacked the tetra-acidic structures present in the glycans from rhEPO. Determination of charge state after treatment of human serum EPO with Arthrobacter ureafaciens sialidase showed that the acidity of the oligosaccharide structures was caused by sialic acids. The sugar profiles of human serum EPO, describing both neutral and charged sugar, appeared significantly different from the profiles of rhEPO. The detection of glycan structural discrepancies between human serum EPO and rhEPO by sugar profiling may be significant for diagnosing pathologic conditions, maintaining pharmaceutical quality control, and establishing a direct method to detect the misuse of rhEPO in sports. IntroductionHuman erythropoietin (EPO) is a glycoprotein that is synthesized mainly in the kidney and that stimulates erythropoiesis through actions on erythroid progenitor cells. [1][2][3] Human EPO (hEPO) was the first hematopoietic growth factor to be cloned. 4,5 Recombinant hEPO (rhEPO) has been available as a drug since 1988 and is used in the clinical treatment of anemia, especially anemia caused by renal failure. In sports the misuse of rhEPO has been suspected among athletes for several years. 6 Active hEPO consists of a single 165-amino acid polypeptide chain with three N-glycosylation sites at Asn24, Asn38, and Asn83, respectively, and one O-glycosylation site at Ser126. The average carbohydrate content is approximately 40%. 7-9 Glycosylation is important for the biologic activity of EPO. Removal or modification of the glycan chains results in altered in vivo and in vitro activity. [9][10][11][12][13][14] Furthermore, the number of sialic acid residues and the branching pattern of the N-linked oligosaccharides modify the pharmacodynamics, speed of catabolism, and biologic activity of hEPO. 11,15,16 Oligosaccharide units, or glycans, of glycoproteins serve a variety of functions, including folding of nascent polypeptide chains in the endoplasmic reticulum, protection of the protein moieties from the action of proteases, and modulation of biologic act...

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Sugar printing rheumatic diseases: A potential method for disease differentiation using immunoglobulin G oligosaccharides

Cited by 74 publications

References 33 publications

Increased Levels of Galactose-Deficient Anti-Gal Immunoglobulin G in the Sera of Hepatitis C Virus-Infected Individuals with Fibrosis and Cirrhosis

Increased Levels of Galactose-Deficient Anti-Gal Immunoglobulin G in the Sera of Hepatitis C Virus-Infected Individuals with Fibrosis and Cirrhosis

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

Sugar profiling proves that human serum erythropoietin differs from recombinant human erythropoietin

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