Network theory of glycosylation--etiologic and pathogenic implications of changes in IgG glycoform levels in autoimmunity.

It is now well established that glycoproteins are populations of individual glycoforms. While it has been inferred from in vitro experiments that the differential glycosylation of glycoproteins diversifies their function, evidence is lacking for such a role in vivo. Alterations in IgG glycosylation in both normal and disease states in vivo, however, provide strong evidence that glycosylation is not static and may be a highly regulated event. The large amount of data correlating disease activity and severity in autoimmune diseases which have a strong B cell component with changes in the incidence of IgG glycoforms, now suggest that glycoform population shifts may not be just a marker of disease activity, but may also contribute directly to disease persistence and pathogenesis.