Immunoglobulin G (IgG) is a central player in various antibody dependent autoimmune pathologies and it has many downstream effector functions involving Fc receptors and complement. N-linked glycans are present both in the conserved N-glycan site located at asparagine 297 on the Fc domain and in 10–20% of the Fab domain, which affects IgG effector functions and antigen binding, respectively. The N-glycans present in IgG-Fc are predominantly consist of a core-fucosylated complex biantennary structure containing 0-2 galactose residues with terminal 𝛼2–6-linked sialic acids and/or a bisecting N-acetylglucosamine (GlcNAc). IgG-Fc glycans regulate its stability and, engagement with both the Fc receptors and complement components. Differential fucosylation, galactosylation and sialylation status of IgG-Fc influence its functional activities significantly. These alterations in N-glycans are dependent on age, sex, genes, activity of the enzymes (glycosyl transferases and glycosidases), immune factors, environmental factors and on different inflammatory conditions. Various IgG-Fc glycoforms are present in the serum of rheumatoid arthritis patients and during pregnancy. Prior to arthritis onset, change towards pro-inflammatory Fc glycosylation phenotype was observed. Modification of N-glycans in IgG-Fc by glyco-engineering or by specific cleavage using Streptococcus pyogenes secreted endoglycosidase (EndoS) attenuated joint inflammation. Similar strategies could be used to treat IgG-dependent inflammation in various target organs. © 2004 - 2023 Nova Science Publishers