Glycans Instructing Immunity: The Emerging Role of Altered Glycosylation in Clinical Immunology

Overview

Journal Front Pediatr

Specialty Pediatrics

Date 2015 Jul 1

PMID 26125015

Citations 32

Authors

Jonathan J Lyons

Joshua D Milner

Sergio D Rosenzweig

Affiliations

Soon will be listed here.

Abstract

Protein glycosylation is an important epigenetic modifying process affecting expression, localization, and function of numerous proteins required for normal immune function. Recessive germline mutations in genes responsible for protein glycosylation processes result in congenital disorders of glycosylation and can have profound immunologic consequences. Genetic mutations in immune signaling pathways that affect glycosylation sites have also been shown to cause disease. Sugar supplementation and in vivo alteration of glycans by medication holds therapeutic promise for some of these disorders. Further understanding of how changes in glycosylation alter immunity may provide novel treatment approaches for allergic disease, immune dysregulation, and immunodeficiency in the future.

Citing Articles

Potential biomarkers and immune infiltration linking endometriosis with recurrent pregnancy loss based on bioinformatics and machine learning.

Chen J, Li Q, Liu X, Lin F, Jing Y, Yang J Front Mol Biosci. 2025; 12:1529507.

PMID: 39963268 PMC: 11830612. DOI: 10.3389/fmolb.2025.1529507.

An Automated Tool for Glycosimilarity Assessment of mAb Therapeutic Biosimilars: Trastuzumab and Bevacizumab as Case Studies.

Shrivastava A, Patil S, Shah R, Rathore A BioDrugs. 2025; 39(2):333-345.

PMID: 39873867 DOI: 10.1007/s40259-025-00704-6.

Transcriptome-wide association study of circulating IgE levels identifies novel targets for asthma and allergic diseases.

Recto K, Huan T, Lee D, Lee G, Gereige J, Yao C Front Immunol. 2023; 14:1080071.

PMID: 36793728 PMC: 9922991. DOI: 10.3389/fimmu.2023.1080071.

Aberrant N-glycosylation in cancer: MGAT5 and β1,6-GlcNAc branched N-glycans as critical regulators of tumor development and progression.

de-Souza-Ferreira M, Ferreira E, de-Freitas-Junior J Cell Oncol (Dordr). 2023; 46(3):481-501.

PMID: 36689079 DOI: 10.1007/s13402-023-00770-4.

Application of StrucGP in medical immunology: site-specific N-glycoproteomic analysis of macrophages.

Li P, Chen Z, You S, Xu Y, Hao Z, Liu D Front Med. 2022; 17(2):304-316.

PMID: 36580234 DOI: 10.1007/s11684-022-0964-8.

References

Partridge E, Le Roy C, Di Guglielmo G, Pawling J, Cheung P, Granovsky M . Regulation of cytokine receptors by Golgi N-glycan processing and endocytosis. Science. 2004; 306(5693):120-4. DOI: 10.1126/science.1102109. View

Marquardt T, Luhn K, Srikrishna G, Freeze H, Harms E, Vestweber D . Correction of leukocyte adhesion deficiency type II with oral fucose. Blood. 1999; 94(12):3976-85. View

Etzioni A, Tonetti M . Fucose supplementation in leukocyte adhesion deficiency type II. Blood. 2000; 95(11):3641-3. View

Brodsky R . Paroxysmal nocturnal hemoglobinuria. Blood. 2014; 124(18):2804-11. PMC: 4215311. DOI: 10.1182/blood-2014-02-522128. View

De Praeter CM , Gerwig G, BAUSE E, Nuytinck L, Vliegenthart J, Breuer W . A novel disorder caused by defective biosynthesis of N-linked oligosaccharides due to glucosidase I deficiency. Am J Hum Genet. 2000; 66(6):1744-56. PMC: 1378052. DOI: 10.1086/302948. View

Zhang Y, Yu X, Ichikawa M, Lyons J, Datta S, Lamborn I . Autosomal recessive phosphoglucomutase 3 (PGM3) mutations link glycosylation defects to atopy, immune deficiency, autoimmunity, and neurocognitive impairment. J Allergy Clin Immunol. 2014; 133(5):1400-9, 1409.e1-5. PMC: 4016982. DOI: 10.1016/j.jaci.2014.02.013. View

Mkhikian H, Grigorian A, Li C, Chen H, Newton B, Zhou R . Genetics and the environment converge to dysregulate N-glycosylation in multiple sclerosis. Nat Commun. 2011; 2:334. PMC: 3133923. DOI: 10.1038/ncomms1333. View

Greig K, Antonchuk J, Metcalf D, Morgan P, Krebs D, Zhang J . Agm1/Pgm3-mediated sugar nucleotide synthesis is essential for hematopoiesis and development. Mol Cell Biol. 2007; 27(16):5849-59. PMC: 1952135. DOI: 10.1128/MCB.00802-07. View

Martin C, Oeser J, Svitek C, Hunter S, Hutton J, OBrien R . Identification and characterization of a human cDNA and gene encoding a ubiquitously expressed glucose-6-phosphatase catalytic subunit-related protein. J Mol Endocrinol. 2002; 29(2):205-22. DOI: 10.1677/jme.0.0290205. View

10.

Banka S, Chervinsky E, Newman W, Crow Y, Yeganeh S, Yacobovich J . Further delineation of the phenotype of severe congenital neutropenia type 4 due to mutations in G6PC3. Eur J Hum Genet. 2010; 19(1):18-22. PMC: 3039503. DOI: 10.1038/ejhg.2010.136. View

11.

Guevara J, Espinosa B, Zenteno E, Vazguez L, Luna J, Perry G . Altered glycosylation pattern of proteins in Alzheimer disease. J Neuropathol Exp Neurol. 1998; 57(10):905-14. DOI: 10.1097/00005072-199810000-00003. View

12.

Chu V, Whittaker G . Influenza virus entry and infection require host cell N-linked glycoprotein. Proc Natl Acad Sci U S A. 2004; 101(52):18153-8. PMC: 535801. DOI: 10.1073/pnas.0405172102. View

13.

Moncada-Velez M, Martinez-Barricarte R, Bogunovic D, Kong X, Blancas-Galicia L, Tirpan C . Partial IFN-γR2 deficiency is due to protein misfolding and can be rescued by inhibitors of glycosylation. Blood. 2013; 122(14):2390-401. PMC: 3790508. DOI: 10.1182/blood-2013-01-480814. View

14.

Ruggiano A, Foresti O, Carvalho P . Quality control: ER-associated degradation: protein quality control and beyond. J Cell Biol. 2014; 204(6):869-79. PMC: 3998802. DOI: 10.1083/jcb.201312042. View

15.

Liu S, Whiting C, Tomassian T, Pang M, Bissel S, Baum L . Endogenous galectin-1 enforces class I-restricted TCR functional fate decisions in thymocytes. Blood. 2008; 112(1):120-30. PMC: 2435683. DOI: 10.1182/blood-2007-09-114181. View

16.

van Kooyk Y, Rabinovich G . Protein-glycan interactions in the control of innate and adaptive immune responses. Nat Immunol. 2008; 9(6):593-601. DOI: 10.1038/ni.f.203. View

17.

Triot A, Jarvinen P, Arostegui J, Murugan D, Kohistani N, Diaz J . Inherited biallelic CSF3R mutations in severe congenital neutropenia. Blood. 2014; 123(24):3811-7. PMC: 4055927. DOI: 10.1182/blood-2013-11-535419. View

18.

Vogt G, Chapgier A, Yang K, Chuzhanova N, Feinberg J, Fieschi C . Gains of glycosylation comprise an unexpectedly large group of pathogenic mutations. Nat Genet. 2005; 37(7):692-700. DOI: 10.1038/ng1581. View

19.

Jaeken J, Hennet T, Matthijs G, Freeze H . CDG nomenclature: time for a change!. Biochim Biophys Acta. 2009; 1792(9):825-6. PMC: 3917312. DOI: 10.1016/j.bbadis.2009.08.005. View

20.

Kjaergaard S, Kristiansson B, Stibler H, Freeze H, Schwartz M, Martinsson T . Failure of short-term mannose therapy of patients with carbohydrate-deficient glycoprotein syndrome type 1A. Acta Paediatr. 1998; 87(8):884-8. DOI: 10.1080/080352598750013680. View