Heterogeneity of IgG Glycosylation in Adult Periodontal Disease

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Heterogeneity of IgG Glycosylation in Adult Periodontal Disease
2005
J. Novak1,*, M. Tomana2, G.R. Shah3, R. Brown1, and J. Mestecky1,2
Journal of Dental Research

© 2005 International and American Associations for Dental Research

1 Departments of Microbiology-Box 1, 2 Medicine, and 3 Oral Diagnostics, University of Alabama at Birmingham, 845 19th Street South, Birmingham, AL 35294-2170;

* corresponding author, jannovak@uab.edu

ABSTRACT

Periodontal disease is a chronic inflammatory disease of bacterial etiology. In many other chronic inflammatory diseases, IgG glycans are galactose-deficient and thus capable of complement activation through the lectin pathway. In this study, we examined whether IgG in serum and gingival crevicular fluid, and IgG locally produced by plasma cells in gingiva of periodontal disease patients, display altered glycosylation. We developed a lectin-ELISA to measure levels of galactose-deficient IgG in the fluids and immunofluorescence staining to detect galactose-deficient IgG-producing cells in gingiva. Our results indicated higher levels of galactose-deficient IgG in sera and gingival crevicular fluid from periodontal disease patients, compared with levels in healthy controls. Furthermore, gingivae from periodontal disease patients exhibited infiltration of IgG-producing plasma cells; many of them contained galactose-deficient IgG in the cytoplasm. Analysis of our data suggests that IgG secreted by B-cells was aberrantly glycosylated, which resulted in the production of pro-inflammatory galactose-deficient IgG.


KEY WORDS: IgG Ô N-glycans Ô periodontal disease Ô galactose deficiency.

INTRODUCTION

Antigens and bacterial products of Gram-negative bacteria associated with periodontal disease (Socransky et al., 1998) induce chronic inflammatory responses in the periodontium, ultimately resulting in the progressive loss of tooth support (for review, see Fujihashi et al., 1993; Kinane et al., 1999).

In many respects, periodontal disease shares some common features with other chronic inflammatory diseases, particularly with rheumatoid arthritis, including: production of IgM and IgA rheumatoid factor (Hirsch et al., 1989); infiltration of inflamed tissue with mainly IgG-secreting plasma cells (Ogawa et al., 1989); production of auto-antibodies to tissue components (collagen II in rheumatoid arthritis; collagens I and III in periodontal disease; Hirsch et al., 1988); similar cytokine profiles (Fujihashi et al., 1993; Pistoia, 1997); and increased levels of IL-6 (Fujihashi et al., 1993; Pistoia, 1997).

Extensive structural studies of IgG molecules produced at the site of chronic inflammation and detectable in the circulation revealed profound alterations in the glycan moieties. Specifically, deficiencies of some monosaccharides, especially galactose on IgG, have been described in human chronic inflammatory diseases, such as rheumatoid arthritis, inflammatory bowel disease, tuberculosis, and infection with HIV (Mullinax and Mullinax, 1975; Parekh et al., 1985 , 1988; Tomana et al., 1988; Bodman et al., 1992; Tsuchiya et al., 1993; Rademacher et al., 1994; Tomana, 1996; Moore et al., 2005). IgG contains one complex-type oligosaccharide (Fig. 1A) per each heavy chain linked to the conserved glycosylation site on asparagine 297 within constant region domain 2, which presumably has a role in maintaining the three-dimensional structure of the Fc portion of IgG. In IgG with galactose-deficient glycans, the terminally exposed sugar molecule is N-acetylglucosamine. Analysis of experimental data has indicated that galactose-deficient IgG is pathogenic (Rademacher et al., 1994): Galactose-deficient IgG binds to the mannan-binding lectin and thus activates the complement cascade by the lectin pathway (Malhotra et al., 1995). Furthermore, glycans on IgG molecules affect binding and internalization by Fc receptors expressed on phagocytic cells (Krapp et al., 2003) and, thus, influence opsonization of antigens by phagocytosis.

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