Antibody glycosylation in autoimmune diseases

Abstract

The glycosylation of the fragment crystallizable (Fc) region of immunoglobulins (Ig) is critical for the modulation of antibody effects on inflammation. Moreover, antibody glycosylation may induce pathologic modifications and ultimately contribute to the development of autoimmune diseases. Thanks to progress in the analysis of glycosylation, more data are available on IgG and its subclass structures in the context of autoimmune diseases. In this review, we focused on the impact of Ig glycosylation in autoimmunity, describing how it modulates the immune response and how glycome profiles can be used as biomarkers of disease activity. The analysis of antibody glycosylation demonstrated specific features in human autoimmune and chronic inflammatory conditions, including rheumatoid arthritis, systemic lupus erythematosus, inflammatory bowel disease and autoimmune liver diseases, among others. Within the same disease, different patterns are associated with disease severity and treatment options. Future research may increase the information available on the distinct glycome profiles and expand their potential role as biomarkers and as targets for treatment, ultimately favoring an individualized approach.

Keywords: Antibody; Autoimmune Diseases; Fc fragment; Glycosylation; Inflammation.

Figure 1.

Immunoregulation pathways of antibody glycosylation in autoimmune diseases. a) increased galactosylation or sialylation of antibodies promotes binding affinity to inhibitory receptor FcγRIIb. Galactosylated, sialylated or fucosylated glycans promote the anti-inflammatory functions of antibody. b) Increased sialylation or fucosylation of antibody promote binding affinity to activating receptor FcγRIIIa, which mediates ADCC; Increased galactosylation of antibodies promotes binding affinity to C1q, which mediates CDC; Increased galactosylation or sialylation of antibody promotes binding affinity to FcγRIIa, which mediates ADCP; Decreased terminal mannose, increased galactosylation or sialylation of antibody promotes binding affinity to FcRn, which determines antibody half-life. Antibody effector functions play a role in initiation, development, and pathology of autoimmune diseases. G0, agalactosylated N-linked glycans; G1/2, singly galactosylated or digalactosylated N-linked glycans; G1, singly galactosylated N-linked glycans; G2, digalactosylated N-linked glycans.