IgG glycosylation in autoimmune diseases

Abstract

Immunoglobulin G (IgG) is the most abundant glycoprotein in human serum. All IgG subclasses have a single-conserved N-linked glycosylation site at Asn297 of the heavy chain and 10–30% of IgGs are N-glycosylated also in a Fab region. N-glycans of Fc are sialylated and fucosylated biantennary complex-type structures. Glycosylation plays a key role in antibody function, and IgG N-glycans are essential for the proper activity of the immune system. Fc glycans are important for IgG effector functions, whereas Fab oligosaccharides modulate antigen binding. Glycosylation changes of IgG are associated with the development of various human diseases, including autoimmune states. The modification of one sugar moiety in N-glycan structure may result in the stimulation or suppression of immune response. The lack of core fucose leads to the enhancement of pro-inflammatory activity, whereas an increase of sialylation determines immunosuppressive properties of IgG. The contribution of IgG Fc glycosylation changes has been demonstrated in the pathogenesis of rheumatoid arthritis, lupus erythematosus and Crohn’s disease. A decrease in IgG galactosylation and sialylation, found in these diseases, activates effector cells and triggers inflammatory reactions. A detailed analysis of changes in IgG glycosylation and their effects on the development of autoimmune diseases is important in the treatment of these diseases. IgGs with modified α2,6-sialylation are used as therapeutic antibodies with anti-inflammatory properties. Numerous studies on IgG glycosylation have provided evidence of the role of this post-translational modification in the proper functioning of antibodies and the importance of changes in the structure of IgG glycans, mainly incomplete galactosylation and desialylation, in the pathogenesis of many diseases. The continuation of these studies may contribute to explaining the mechanisms of autoimmunity that is still poorly understood.

The Role of Irisin in Cancer Disease

“…Tissue-specific and cell-specific enzymes of the endoplasmic reticulum and the Golgi apparatus participate in the glycosylation process. Proteins can be modified in the process of N-glycosylation and/or O-glycosylation [25]. The N-glycans and O-glycans formed by glycosylation affect the physicochemical properties of proteins, which determines their role in metabolic processes [26].…”

“…The N-glycans and O-glycans formed by glycosylation affect the physicochemical properties of proteins, which determines their role in metabolic processes [26]. N-Linked glycoproteins are created by the formation of a glycosidic bond between N-acetylglucosamine (GlcNAc) and the nitrogen originating from the amide group of asparagine (Asn) in the sequence Asn-X-Ser/Thr (X being any amino acid except proline) [24,25]. In oncogenesis, abnormal glycosylation is one of the key factors in tumor development.…”

Variability of serum IgG sialylation and galactosylation degree in women with advanced endometriosis

“…Glycosylation, one of the most common post-translational modifications of secretory and membrane proteins, plays an important role in biological processes, such as cell recognition and adhesion, cell–cell communication and cell–cell interactions 17 , and plays a key role in antibodies function 18 . Immunoglobulin G (IgG), 150-kDa glycoprotein, is the most abundant immunoglobulin in blood (represents about 75% of serum immunoglobulins), involved in the pathogenesis and progression of many diseases.…”

“…The contribution of IgG Fc glycosylation changes was documented for the pathogenesis of rheumatoid arthritis, Crohn’s disease and lupus erythematosus. Found in these diseases the decreased IgG galactosylation and sialylation, activates effector cells and initiates an inflammatory response 18 . IgG has one biantennary N-linked glycan attached to asparagine 297 14 , 21 , which consists of a constant heptameric core structure containing three mannose residues and four GlcNAc residues and may contain additional core fucose, as well as bisecting GlcNAc.…”

The Contribution of IgG Glycosylation to Antibody-Dependent Cell-Mediated Cytotoxicity (ADCC) and Complement-Dependent Cytotoxicity (CDC) in Hashimoto’s Thyroiditis: An in Vitro Model of Thyroid Autoimmunity

“…Modifications of Fc N-glycan structures are commonly used in therapeutic antibodies to modulate the efficiency of Fc binding to its receptor and to increase the effectiveness of therapy [11]. Changes of IgG N-glycosylation have been noted in different chronic diseases, including cancers [12,13] and inflammatory disorders [14][15][16][17]. Although analysis of IgG glycosylation has become a standard approach in work aimed at discovering new plasma biomarkers, functional analysis of altered IgG glycosylation remains largely neglected.…”