Twin studies on the effect of genetic factors on serum agalactosyl immunoglobulin G levels

Abstract

Abstract. The level of immunoglobulin G (IgG) lacking the terminal galactose, referred to as agalactosyl IgG, was found to be increased in chronic inflammatory diseases, such as rheumatoid arthritis and inflammatory bowel disease (IBD), particularly in Crohn's disease, which is suggested to have a genetic component. This oligosaccharide modification of IgG is mainly regulated by the expression of glyco-genes; however, the association between genetic factors and changes in the IgG glycosylation has not been fully elucidated. The aim of the present study was to assess the role of genetics in this process by comparing the serum agalactosyl IgG levels between members of monozygotic and dizygotic twin pairs who underwent medical check-ups at the same time. The serum agalactosyl IgG level was assayed using high-performance liquid chromatography. Hematological and biochemical markers, including γ-glutamyltranspeptidase (γGTP), alanine aminotransferase (ALT) and white blood cell (WBC) count, were also measured. Although the serum γGTP levels (and, to a lesser extent, ALT and WBC levels) exhibited a correlation within monozygotic twin pairs, agalactosyl IgG levels were not found to be correlated between members of either type of twin pairs. Thus, the role of genetic factors in determining serum agalactosyl IgG levels may be less significant compared to the effect of environmental factors or the onset of inflammatory disease.

Tertiary Lymphoid Structures: Autoimmunity Goes Local

“…Agalactosylated IgG levels were not found to be correlated in twin pairs indicating a low influence from genetic factors for IgG glycosylation ( 338 ). However, four loci contained genes for glycosyltransferases (ST6GAL1, B4GALT1, FUT8, and MGAT3) have been highlighted in genome-wide association studies for loci associated with IgG N-glycosylation ( 339 ).…”

The N-Glycosylation of Mouse Immunoglobulin G (IgG)-Fragment Crystallizable Differs Between IgG Subclasses and Strains

“…Furthermore, as IgG Fc-glycosylation is partly genetically determined (18) and partly influenced by environmental factors like exposure to immunological challenges (19), baseline Fc-glycosylation may play a role in the outcome of an immunological study, and may confound the potential translation to the human situation. Differences in total plasma N -glycosylation between mouse strains were demonstrated before (20).…”

“…Contrary to the human IgG Fc-glycosylation, mice predominantly express the sialic acid N -glycolylneuraminic acid (Neu5Gc), while humans exclusively express N -acetylneuraminic acid (Neu5Ac) ( 17 ). Furthermore, as IgG Fc-glycosylation is partly genetically determined ( 18 ) and partly influenced by environmental factors like exposure to immunological challenges ( 19 ), baseline Fc-glycosylation may play a role in the outcome of an immunological study, and may confound the potential translation to the human situation. Differences in total plasma N -glycosylation between mouse strains were demonstrated before ( 20 ).…”