Blood group B glycosphingolipids in α-galactosidase deficiency (Fabry disease): influence of secretor status

• Published in: Biochimica et biophysica acta Vol. 1345; no. 2; pp. 180 - 187
• Main Authors: Ledvinová, Jana, Poupětová, Helena, Hanáčková, Alžběta, Pı́sačka, Martin, Elleder, Milan
• Format: Journal Article
• Language: English
• Published: Netherlands Elsevier B.V 01.04.1997
• Subjects: ABO Blood-Group System - blood; ABO Blood-Group System - urine; Adult; Animals; Antibodies, Monoclonal - immunology; Blood group B secretor; Chromatography, Thin Layer; Fabry disease; Fabry Disease - blood; Fabry Disease - urine; Glycosphingolipid antigen; Glycosphingolipids - analysis; Glycosphingolipids - chemistry; Glycosphingolipids - immunology; Glycosphingolipids - metabolism; Humans; Kidney Transplantation; Mice; Palatine Tonsil - chemistry; Reference Values; Time Factors; Tonsil; Urinary sediment; α-Galactosidase deficiency; Urinary sediment; Tonsil; B gene, blood group B gene; HPTLC, high-performance thin-layer chromatography; Gg 4Cer (or GA1), asialoGM1 ganglioside; mAbs, monoclonal antibodies; Fabry disease; Glycosphingolipid antigen; Ga 2Cer, galabiosylceramide; LacCer, lactosylceramide; LSIMS, liquid-secondary ion mass spectrometry; Gb 4Cer, globoside; Gb 3Cer, globotriaosylceramide; α-Galactosidase deficiency; HGC, hexaglycosylceramide; Se gene, secretor gene; GSL, glycosphingolipids; Blood group B secretor; GlcCer, glucosylceramide; B-GSL, glycosphingolipids with blood group B determinant; B-6 (or A-6), shortened designation for hexaglycosylceramide with blood group B (or A) determinant based on both types of oligosaccharide chain: type 1 (B-6-1, IV 2- α-fucosyl-IV 3- α-galactosyl-lactotetraglycosylceramide): Gal α1→3Gal(2←1Fuc) β1→3GlcNAc β1→3Gal β1→4Glc β1→1́Cer; type 2 (B-6-2, IV 2- α-fucosyl-IV 3- α-galactosyl-neolactotetraglycosylceramide): Gal α1→3Gal(2←1Fuc) β1→4GlcNAc β1→3Gal β1→4Glc β1→1́Cer (terminal monosaccharide in A determinant is GalNAc α instead of Gal α); Neutral glycosphingolipids are abbreviated according to the recommendation of the IUPAC-IUB Commission on Biochemical Nomenclature Eur. J. Biochem. 79, 11–21
• ISSN: 0005-2760; 0006-3002; 1879-145X
• DOI: 10.1016/S0005-2760(96)00175-0

Defect in degradation of blood group B-immunoactive glycosphingolipids in Fabry disease (deficiency of lysosomal α-galactosidase EC 3.2.1.22) has been studied using highly sensitive and specific TLC-immunostaining analysis of urinary sediments and tonsillar tissues of blood group B patients and healthy controls, secretors and nonsecretors. The B glycolipid antigens with hexasaccharide chains were consistently found increased (25- to 100-fold) in the urinary sediments of three Fabry patients, blood group B or AB secretors. Conversely, they were absent in the urinary sediment of one blood group B nonsecretor patient. In normal secretors, B glycosphingolipids were present only in traces. Moreover, significant increase in B glycolipid antigens (8-fold) was found in the tonsillar tissue of a Fabry patient blood group B secretor. We conclude that the secretor status is responsible for increased concentration of blood group B glycosphingolipids in both urinary cells and tonsils in α-galactosidase deficiency. The quantity of stored B-immunoactive glycosphingolipids, however, is much lower than that of the mainly accumulated glycosphingolipid Gb 3Cer. The results clearly indicate that active or silent Se gene, which controls synthesis of B-antigen precursors, is responsible for notable difference in B-glycosphingolipids expression in Fabry patients – secretors and nonsecretors. Whether this novel aspect may be of prognostic significance, remains to be established. © 1997 Elsevier Science B.V. All rights reserved.