Glycosylation of Serum Proteins in Inflammatory Diseases

Abstract

Inflammatory diseases are accompanied by numerous changes at the site of inflammation as well as many systemic physiological and biochemical changes. In the past two decades more and more attention is being paid to changes in glycosylation and in this review we describe some of the changes found on main serum proteins (α1-acid glycoprotein, immunoglobulin G, immunoglobulin A, transferrin, haptoglobin, α2-macroglobulin, C-reactive protein, and others). Molecular background and physiological importance of most of these changes are yet to be discovered, but it is evident that glycosylation plays an important role in the inflammatory response. Maybe the greatest value of these changes currently lays in their potential diagnostic and prognostic usage, either in combination with current diagnostic markers or on their own. However, determining glycan structures is still technically too complex for most clinical laboratories and further efforts have to be made to develop simple analytical tools to study changes in glycosylation.

GlycA: A Composite Nuclear Magnetic Resonance Biomarker of Systemic Inflammation

“…Unlike existing biomarkers of inflammation that are discrete molecular species, such as acute-phase proteins or inflammatory cytokines, GlycA is a composite biomarker that senses the integrated concentrations and glycosylation states of several of the most abundant acute-phase proteins in serum. We speculate that GlycA concentrations may therefore provide a more stable measure of low-grade systemic inflammation and respond more uniformly to diverse inflammatory stimuli than individual acute-phase reactants that are each regulated differentially and vary in response to inflammation site and intensity (2,3 ).…”

“…Virtually all of the abundant proteins in serum, with the exception of albumin, are N-linked glycoproteins, and the great majority of these are acute-phase proteins that rise or fall in response to acute and chronic inflammatory stimuli (2,3 ). The major mediator of the acute-phase response is interleukin-6 (IL-6), 5 which induces hepatic synthesis and secretion of positive acute-phase serum proteins such as ␣ 1 -acid glycoprotein, haptoglobin, and ␣ 1 -antitrypsin and reduces levels of negative acute-phase proteins such as transferrin (2,4 ).…”

“…The N-linked acute-phase glycoproteins have carbohydrate structures with 2 to 4 branches (diantennary, triantennary, and tetra-antennary). Inflammation-or disease-induced alterations of these structures include changes in the number of antennary branches and the identities of the terminal saccharide residues resulting primarily from addition or removal of sialic acid, galactose, or fucose residues (3,5,6 ). Such modifications of glycosylation microheterogeneity can redirect glycopro-teins to different cellular and tissue receptors and change their functions (3,5 ).…”

Veterinary Biomarker Discovery: Proteomic Analysis of Acute Phase Proteins

“…A remarkable feature of AGP is the microheterogeneity of its sugar moieties and the modification of these sugars during disease. AGP has five N-linked complex type glycans which may be present as bi-, tri-, and tetra-antenary structures (Gornik et al, 2008). Studies have indicated significant enhancement of bi-antennary complex glycans and alpha-1-3fucosylated bi-, tri-, and tetra-antennary glycans, as well as decreases in tri-antennary glycans of AGP, in patients with inflammatory diseases.…”

Chromatographic Monoliths for High-Throughput Immunoaffinity Isolation of Transferrin from Human Plasma

“…[5] Glycosylation is involved in essential cell processes including signalization, interaction and recognition of cells. [6] Therefore, it is not strange that changes in glycosylation patterns are related to congenital disorders of glycosylation, [7][8][9] cancer, [10] different autoimmune [11] and inflammatory diseases [12] and have a high potential as diagnostic and prognostic disease biomarkers. [13] To meet the demand of determining normal and aberrant biological glycosylation patterns of individual and total glycoproteins from body fluids and tissues in different human populations, methods for glycan analysis of large number of samples (so called high-throughput methods) are being extensively developed in recent years.…”