Identification of Distinct Glycoforms of IgA1 in Plasma from Patients with Immunoglobulin A (IgA) Nephropathy and Healthy Individuals

Promoters of Human Cosmc and T-synthase Genes Are Similar in Structure, Yet Different in Epigenetic Regulation

“…Studies suggest that a deficiency of galactose in the O-glycans and concomitant expression of the Tn antigen or STn in the hinge region of IgA1 might be responsible for initiating the pathogenesis (15,23,(71)(72)(73)(74) of IgAN in patients. However, we recently identified two distinct glycoforms as follows: the major fraction of IgA1 has normal O-glycans, and the minor fraction carries Tn/STn antigens in the plasma from both patients with IgAN and healthy controls (22), suggesting a more complex role of Tn/STn antigens on IgA1 in the disease. Several studies showed that the transcript levels of Cosmc and/or T-synthase are reduced in the B cells of patients with IgAN (24 -26, 76 -78).…”

“…Galactosedeficient O-glycans or Tn/STn antigens are commonly found in the hinge region of immunoglobulin A1 (IgA1) molecules from sera of patients with IgAN, and they also occur in serum IgA1 from normal individuals in our study (22). Although the mechanism underlying a fraction of IgA1 from both healthy controls and IgAN patients carrying Tn/STn antigens is not fully understood, several studies have shown that under-galactosylated IgA1 is associated with a lower transcription level of Cosmc and T-synthase in peripheral B cells or immortalized B cells from patients with .…”

N-glycopeptide Signatures of IgA2 in Serum from Patients with Hepatitis B Virus-related Liver Diseases

“…IgA nephropathy is histologically characterized by the deposition of IgA 1 with undergalactosylation of O-glycans. However, these glycoforms in IgA 1 are not restricted to IgA nephropathy (38). Prior research has suggested that Igs, including IgA, are the major glycoproteins involved in the modification of total serum N-glycome in LC (39,40).…”

Glyco-engineering for the production of recombinant IgA1 with distinct mucin-type O-glycans in plants

“…Several studies showed that the galactose-deficient version of IgA1 leads to the formation of immune complexes and therefore has a critical impact on the pathogenesis of IgAN 18,19 . In contrast, a recent study concluded that the expression of the Tn antigen alone was not sufficient to cause the disease as it was found in patients as well as in healthy individuals and only the level of the total IgA1 concentration in plasma differed significantly between disease and non-disease suggesting that the overexpression of galactose-deficient IgA1 is critical for the disease progression 16 . Due to these inconsistent data, additional studies are needed to investigate the contribution of the galactose-deficient IgA1 O-glycans and antiglycan antibody immune complex formation to disease pathogenesis.…”