IgG Fc N-glycosylation: Alterations in neurologic diseases and potential therapeutic target?. (January 2019)

• Record Type: Journal Article
• Authors: Kronimus, Yannick; Dodel, Richard; Galuska, Sebastian P.; Neumann, Sascha
• Is Part Of: Journal of autoimmunity. Volume 96(2019)
• Page Start: 14
• Page End: 23
• Publication Date: 2019-01
• Subjects: Immunoglobulin G (IgG) -- Fc N-glycosylation -- Effector function -- Naturally occurring antibodies (nAbs) -- Glycoengineering; Autoimmunity -- Periodicals; Autoimmune diseases -- Periodicals; Autoantibodies -- Periodicals; Autoimmune Diseases -- Periodicals; Auto-immunité -- Périodiques; Maladies auto-immunes -- Périodiques; Electronic journals; 616.978005
• DOI: 10.1016/j.jaut.2018.10.006
• Languages: English
• ISSNs: 0896-8411

Abstract

Abstract: Immunoglobulin G (IgG) is the most abundant antibody subclass of the human circulatory system and has important functions in the adaptive immune response. On the one hand, recognition and neutralization of antigens is mediated by the fab fragment, and on the other hand, processes such as phagocytosis, complement activation and inflammatory reactions are triggered by the Fc fragment. Here, the composition of conserved N-glycans attached to asparagine 297 of the IgG CH2 domain is a major critical factor that particularly modulates the effector functions of IgG. Additional attachments of fucoses, galactoses, N -acetylglucosamines, and sialic acids have been identified as factors that influence the affinity to a wide range of complement proteins and receptors and, thus, secondarily induce the secretion of pro- and anti-inflammatory cytokines. Consequently, alterations in the IgG Fc N-glycosylation pattern can provoke disruptions in the immunological state and are accompanied by various diseases, although the involvement of changed IgG glycosylation in disease outbreaks remains unknown. In addition to many autoimmune diseases, which have already been extensively reviewed, there are a number of further disorders related to altered IgG glycosylation patterns. In the present review, we focus on neurologic diseases, as in the last few years, an increasing number of studies have been published in this field. Due to the absence of reliable early biomarkers as well as therapeutic options in many cases, such analyses are of great interest and reveal possible future approaches. Highlights: Diverse autoimmune neurologic disorders are accompanied with altered IgG Fc N-glycosylation patterns. Composition of IgG Fc N-glycans affect various antibody effector functions. Altered IgG Fc N-glycosylation patterns may represent future therapeutic and diagnostic targets. Glycoengineering may fine-tune the function of therapeutic antibodies.