Here, we want to investigate the genetic susceptibility, IL-6 dependency and functional relevance of pro-inflammatory glycosylated IgGs in autoimmunity. It becomes more and more clear that the Fc glycosylation pattern at asparagine (Asn) 297 of IgG antibodies determines their pro- or anti-inflammatory effector functions. Pro-inflammatory immune responses induce pro-inflammatory de-galactosylated (G0) IgGs, whereas tolerance induces galactosylated and sialylated immunosuppressive IgGs. The ratio of differentially glycosylated antigen-specific IgGs finally determines a pro- or anti-inflammatory humoral immune response by targeting different compositions of FcgRs and/or glycan binding c-type lectin receptors. Accordingly, autoantigen-specific serum IgGs from patients with rheumatoid arthritis (RA) or the autoimmune skin disease bullous pemphigoid (BP), respectively, are to a high extent de-galactosylated (G0). The extent of G0 IgG correlates with the disease severity in RA and reverses during remission by e.g. anti-TNF therapy. Thus, IgG Fc glycosylation seems to be a very promising and easy to analyze parameter of the adaptive immune system to detect disease/inflammation states