Immunoglobulin glycosylation in atopic children

Pezer, Marija (2013) Immunoglobulin glycosylation in atopic children. Doctoral thesis, Faculty of Science > Department of Biology.

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Abstract

Immunoglobulin G (IgG) is considered one of modulators of immune response in atopic diseases, most often through interactions with Fcγ receptors (FcγR) on the surface of immune effector cells, and especially with the inhibitory receptor FcγRIIB. Differential N-glycosylation of IgG Fc regions affects the IgG affinity for FcγR, and thus maybe represents one of regulatory mechanisms of immune response in atopic diseases. Children's total plasma N-glycome (TPNG) and IgG N-glycome differ in composition and age dynamics from those found in adults, requiring independent N-glycome analyses of the two populations. To verify the existence of an association between a specific IgG N-glycoprofile and atopic diseases in pediatric population, this study examined TPNG and IgG N-glycoprofile in atopic vs. healthy children. Peripheral blood was collected from 61 patients and 74 healthy controls of both sexes aged 5-18 years. Plasma was separated by centrifugation and IgG isolated by affinity chromatography using protein G. TPNG was examined by hydrophilic interaction high performance liquid chromatography, and IgG N-glycome by hydrophilic interaction ultra performance liquid chromatography. A protein specific IgG N-glycosylation profile different from the one in healthy children was found. The content of majority of simple, smaller, asialylated structures in total IgG N-glycome was smaller and the content of greater, mainly sialylated complex structures was mostly greater in children with atopy. The content of sialylated (especially disialylated), digalactosilated and core fucosylated (mostly without GlcNAc) structures was greater, while the content of agalactosylated and the content of structures with bisecting GlcNAc was smaller in comparison with healthy children, displaying a glycoprofile in principle opposite from the one usually observed in IgG and other proteins in inflammatory conditions. The analysis of IgG N-glycoslyation thus has the potential to be developed into a predisposition, diagnostic and/or prognostic biomarker for atopic diseases in children, and provides a ground for further research in the area, aiming at the development of novel class of biological therapeutics for the treatment of atopic diseases.

Item Type: Thesis (Doctoral thesis)
Keywords: allergy, atopy, immunoglobulin G, glycosylation, N-glycome, pediatric population
Supervisor: Turkalj, Mirjana and Lauc, Gordan
Date: 2013
Number of Pages: 224
Subjects: NATURAL SCIENCES > Biology
Divisions: Faculty of Science > Department of Biology
Depositing User: Grozdana Sirotic
Date Deposited: 10 Feb 2014 14:10
Last Modified: 22 Sep 2014 19:14
URI: http://digre.pmf.unizg.hr/id/eprint/401

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