Band 3 glycoprotein and glycophorin A from erythrocytes of children with congenital disorder of glycosylation type-Ia are underglycosylated

Abstract

Band 3 and PAS-1 (a dimer of glycophorin A) from erythrocyte membranes of three children with congenital disorder of glycosylation, type Ia (CDG-Ia), aged 1 month, 3 years and 10 years respectively, were examined by a new technique that allowed determination of carbohydrate molar composition of glycoproteins separated by sodium dodecyl sulfate polyacrylamide gel electrophoresis. In CDG children a single N-glycan of band 3 glycoprotein was hypoglycosylated and its mannose content was normal or elevated. Glycophorin A which is the major carrier of erythrocyte sialic acid, was deficient in N-acetylgalactosamine, and sialic acid residues. This finding indicated a partial unglycosylation of O-glycans in glycophorin A. In keeping with the results of PAS-1 analysis, total sialic acid in erythrocyte membranes from CDG children was reduced to 40-56% of normal values. A possible molecular mechanism of hypo- and unglycosylation of band 3 and glycophorin A, respectively, in CDG is discussed.

Erythrocyte membranes from a patient with congenital dyserythropoietic anaemia type I (CDA‐I) show identical, although less pronounced, glycoconjugate abnormalities to those from patients with CDA‐II (HEMPAS)

“…It has been postulated that anaemia in CDA‐II may be as a result of clustering of hypoglycosylated and consequently poorly soluble band 3 in erythroblasts that would produce disorganization of their plasma membrane and adversely affect cell, but not necessarily nuclear, division ( Fukuda, 1999). In the presently reported case of CDA‐I, hypoglycosylation of band 3 is minor and cannot be the cause of dyserythropoiesis, as the band 3's from cord and carbohydrate‐deficient glycoprotein (CDG) erythrocytes have an even larger deficit of carbohydrates with 20–22 glycosyl residues/mol, but do not result in ensuing anaemia ( Zdebska et al 2000 ). Thus, it is more probable that, in CDA‐I, dyserythropoiesis and, more precisely, a defective karyokinesis in erythroblasts with the associated disturbance of the cell cycle produce glycoconjugate abnormalities, not vice versa .…”

Abnormal Glycosylation of Red Cell Membrane Band 3 in the Congenital Disorder of Glycosylation Ig

“…Apart from this study, glycosylation abnormalities of band 3 were reported only in CDG Ia (9) and CDG IIa (8). No hematological signs were recorded.…”

“…In contrast, this glycoprotein is partly unglycosylated (nonglycosylated) in CDG Ia (9) and in several patients with CDA I and CDA II (15,29,30). In all these cases, glycosylation of band 3 was reduced.…”

Interaction of glycophorin A with lectins as measured by surface plasmon resonance (SPR).

“…The latter has been described, i.e. human glycophorin A was shown to be underglycosylated in CDG patients (Krotkiewska et al, 1999;Zdebska et al, 2001).…”