Sweet and sour: the impact of sugars on disease

Abstract

The clinical relevance of glycobiology has become the focus of considerable research, as the role of glycosylation in the development, regulation and progression of disease is, slowly but surely, being unveiled. Recent strides in the design and refinement of analytical techniques-sugar profiling, glyco-arrays and functional studies-have helped us gain a better understanding of the complexity and richness of diversity that bestow sugars with an unsurpassed, biospecific coding capacity. Cracking this 'sugar code', and unravelling the structural frameworks and recognition strategies of sugar-based interactions in biological systems that relate to both health and disease, holds tremendous promise for deciphering disease mechanisms. It will also provide a cutting edge potential for the development of novel diagnostic and therapeutic interventions.

Terminal monosaccharide screening of synovial immunoglobulins G and A for the early detection of rheumatoid arthritis

“…Many authors have reported that the majority of the glycosylation changes in RA are related to the degree of glycan branching and the type of substitution of the N-linked glycans with sialic acid and/or fucose [5]. Our previous and present results suggest that the glycosylation proWle of Wbronectin [29], as well as of IgG and IgA, was quite diVerent in early and advanced RA.…”

“…The alterations in IgG proWle are conWned to changes in the level of terminal galactose and number of antennas as well as in the relative proportions of sialic acid, fucose, and bisecting GlcNAc (reviewed in [3][4][5]). In RA, there is an increase in the number of oligosaccharide structures that lack the terminal galactose residue [3,5]. GlycomodiWcations of IgG molecules have been shown to aVect various eVector functions (i.e.…”

“…GlycomodiWcations of IgG molecules have been shown to aVect various eVector functions (i.e. immune complex formation, activation of complement, and binding to monocytes) and to have a critical role in the regulation of the immune response [5].…”

“…For the characterization of RA it is very important to distinguish between early and advanced RA stages and to determine progression and remission periods. Since the glycosylation of glycoproteins is sensitive to alterations in cellular function, changes in glycosylation can be used as a diagnostic value in a number of diseases, including rheumatoid arthritis [4][5][6]. A decreased level of glycan galactosylation in serum and synovial Xuid IgG is known to be associated with disease progression and is used as a prognostic indicator for RA.…”

“…A decreased level of glycan galactosylation in serum and synovial Xuid IgG is known to be associated with disease progression and is used as a prognostic indicator for RA. Patients with arthritis and high levels of hypogalactosylated IgG have poor prognosis [4][5][6][7]. Finally, Pasek et al [8] and Croce et al [9] provided experimental evidence that the treatment of the RA patients with methotrexate or a combination of methotrexate and inXiximab also improves the degree galactosylation of serum IgG and, in their opinion, the analysis of IgG galactosylation in RA patients may have clinical relevance.…”