Impact of autoantibody glycosylation in autoimmune diseases

Objective: Recent outcomes enhanced the critical role of glycosylation pattern of autoantibodies in the pathophysiology of antibody-mediated autoimmune diseases. In this review, we discuss the critical role of immunoglobulin (Ig) glycosylation on skewing immune response towards a pro- or anti-inflammatory pathway.Methods: A comprehensive search of Pubmed references was completed by hand searching of selected articles.Results: We first described the impact of glycosylation on Ig immune effector functions: antibody-dependent cell-mediated cytotoxicity, complement activation, dendritic cell, macrophage or B-cell activation and maturation, neoantigen formation, or Ig-receptor binding. We then reviewed autoimmune diseases with abnormal Ig glycosylation, trying to understand its role in the pathogenic process. We then discussed the usefulness of monitoring Ig glycosylation as a biomarker of disease activity, as demonstrated in proteinase-3 anti-neutrophil cytoplasmic autoantibodies associated vasculitis. After reporting environmental and immune factors known to affect Ig glycosylation process, we finally evoked therapeutic strategies currently being developed in order to modulate Ig glycosylation pattern and autoimmune disease evolution.Conclusion: This overview on Ig glycosylation mechanisms and impact on immune system modulation is necessary to face new therapeutic approaches of autoimmune diseases.