title: Glycans in the immune system and The Altered Glycan Theory of Autoimmunity: a critical review.
abstract: Herein we will review the role of glycans in the immune system. Specific topics covered include: the glycosylation sites of IgE, IgM, IgD, IgE, IgA, and IgG; how glycans can encode "self" identity by functioning as either danger associated molecular patterns (DAMPs) or self-associated molecular patterns (SAMPs); the role of glycans as markers of protein integrity and age; how the glycocalyx can dictate the migration pattern of immune cells; and how the combination of Fc N-glycans and Ig isotype dictate the effector function of immunoglobulins. We speculate that the latter may be responsible for the well-documented association between alterations of the serum glycome and autoimmunity. Due to technological limitations, the extent of these autoimmune-associated glycan alterations and their role in disease pathophysiology has not been fully elucidated. Thus, we also review the current technologies available for glycan analysis, placing an emphasis on Multiple Reaction Monitoring (MRM), a rapid high-throughput technology that has great potential for glycan biomarker research. Finally, we put forth The Altered Glycan Theory of Autoimmunity, which states that each autoimmune disease will have a unique glycan signature characterized by the site-specific relative abundances of individual glycan structures on immune cells and extracellular proteins, especially the site-specific glycosylation patterns of the different immunoglobulin(Ig) classes and subclasses.
authors.affiliation: Department of Dermatology, University of California, Davis School of Medicine, 3301 C Street, Suite 1400, Sacramento, CA 95816, USA. Electronic address: emaverakis@ucdavis.edu.
authors.forename: Emanual
authors.initials: E
authors.lastname: Maverakis
authors.affiliation: Department of Public Health Sciences, Division of Biostatistics, University of California, Davis Medical Center, Sacramento, CA 95816, USA.
authors.forename: Kyoungmi
authors.initials: K
authors.lastname: Kim
authors.affiliation: Department of Dermatology, University of California, Davis School of Medicine, 3301 C Street, Suite 1400, Sacramento, CA 95816, USA.
authors.forename: Michiko
authors.initials: M
authors.lastname: Shimoda
authors.affiliation: Department of Internal Medicine, Division of Rheumatology, University of California, Davis School of Medicine, Sacramento, CA 95817, USA.
authors.forename: M Eric
authors.initials: ME
authors.lastname: Gershwin
authors.affiliation: Department of Dermatology, University of California, Davis School of Medicine, 3301 C Street, Suite 1400, Sacramento, CA 95816, USA.
authors.forename: Forum
authors.initials: F
authors.lastname: Patel
authors.affiliation: Department of Dermatology, University of California, Davis School of Medicine, 3301 C Street, Suite 1400, Sacramento, CA 95816, USA.
authors.forename: Reason
authors.initials: R
authors.lastname: Wilken
authors.affiliation: Department of Internal Medicine, Division of Rheumatology, University of California, Davis School of Medicine, Sacramento, CA 95817, USA.
authors.forename: Siba
authors.initials: S
authors.lastname: Raychaudhuri
authors.affiliation: Department of Public Health Sciences, Division of Biostatistics, University of California, Davis Medical Center, Sacramento, CA 95816, USA.
authors.forename: L Renee
authors.initials: LR
authors.lastname: Ruhaak
authors.affiliation: Department of Chemistry, University of California, Davis, One Shields Avenue, Davis, CA 95616, USA.
authors.forename: Carlito B
authors.initials: CB
authors.lastname: Lebrilla
mesh_terms: D001327:Autoimmune Diseases / Q000276:immunology / Q000378:metabolism / Q000473:pathology; D015551:Autoimmunity / Q000276:immunology*; D001665:Binding Sites / Q000276:immunology; D006031:Glycosylation; D006801:Humans; D007107:Immune System / Q000166:cytology / Q000276:immunology* / Q000378:metabolism; D007136:Immunoglobulins / Q000276:immunology* / Q000378:metabolism; D018448:Models, Immunological; D011134:Polysaccharides / Q000276:immunology* / Q000378:metabolism
chemical_list: D007136:Immunoglobulins; D011134:Polysaccharides
keywords: Autoimmunity; Glycan; Glycome; Glycosylation; Immunoglobulin