Pemphigus-Associated Desmoglein-Specific IgG1 and IgG4 Have a Dominant Agalactosylated Glycan Modification

Aberrant glycan modifications have been hypothesized to drive autoimmune pathogenesis, especially those at the conserved immunoglobulin constant heavy chain domain 2 (CH2)-84.4 site of IgG ( Maverakis et al., 2015 Maverakis E. Kim K. Shimoda M. Gershwin M.E. Patel F. Wilken R. et al. Glycans in the immune system and The Altered Glycan Theory of Autoimmunity: a critical review. J Autoimmun. 2015; 57: 1-13 Crossref PubMed Scopus (343) Google Scholar ). Glycans at this site dictate Ig effector function, with agalactosylated glycans being linked to antibody-mediated autoimmune conditions such as rheumatoid arthritis ( Gudelj et al., 2018 Gudelj I. Salo P.P. Trbojević-Akmačić I. Albers M. Primorac D. Perola M. et al. Low galactosylation of IgG associates with higher risk for future diagnosis of rheumatoid arthritis during 10 years of follow-up. Biochim Biophys Acta Mol Basis Dis. 2018; 1864: 2034-2039 Crossref PubMed Scopus (62) Google Scholar ). Pemphigus vulgaris is an autoimmune blistering disease characterized by autoantibodies directed against desmosomal cadherins.