Specific storage of glycoconjugates with terminal α-galactosyl moieties in the exocrine pancreas of Fabry disease patients with blood group B
| Autor: | Ludovit Skultety, Helena Hulkova, Vladimír Havlíček, Robert Dobrovolný, Ladislav Kuchar, Jitka Rybová, Befekadu Asfaw, Jana Ledvinová, Jakub Sikora |
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| Rok vydání: | 2017 |
| Předmět: |
0301 basic medicine
Male Pathology medicine.medical_specialty Cell type Glycoconjugate Acinar Cells Biochemistry Glycosphingolipids Lipofuscin ABO Blood-Group System 03 medical and health sciences chemistry.chemical_compound Biosynthesis ABO blood group system Insulin-Secreting Cells medicine Humans Pancreas chemistry.chemical_classification geography geography.geographical_feature_category Galactose Middle Aged Islet medicine.disease Fabry disease 030104 developmental biology medicine.anatomical_structure chemistry Case-Control Studies Fabry Disease lipids (amino acids peptides and proteins) |
| Zdroj: | Glycobiology. 28(6) |
| ISSN: | 1460-2423 |
| Popis: | Blood group B glycosphingolipids (B-GSLs) are substrates of the lysosomal alpha-galactosidase A (AGAL). Similar to its major substrate-globotriaosylceramide (Gb3Cer)-B-GSLs are not degraded and accumulate in the cells of patients affected by an inherited defect of AGAL activity (Fabry disease-FD).The pancreas is a secretory organ known to have high biosynthesis of blood group GSLs. Herein, we provide a comprehensive overview of the biochemical and structural abnormalities in pancreatic tissue from two male FD patients with blood group B. In both patients, we found major accumulation of a variety of complex B-GSLs carrying predominantly hexa- and hepta-saccharide structures. The subcellular pathology was dominated by deposits containing B-glycoconjugates and autofluorescent ceroid. The contribution of Gb3Cer to the storage was minor. This abnormal storage pattern was specific for the pancreatic acinar epithelial cells. Other pancreatic cell types including those of islets of Langerhans were affected much less or not at all.Altogether, we provide evidence for a key role of B-antigens in the biochemical and morphological pathology of the exocrine pancreas in FD patients with blood group B. We believe that our findings will trigger further studies aimed at assessing the potential pancreatic dysfunction in this disease. |
| Databáze: | OpenAIRE |
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