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Chimerism after Liver Transplantation for Type IV Glycogen Storage Disease and Type 1 Gaucher's Disease

Starzl, TE and Demetris, AJ and Trucco, M and Ricordi, C and Ildstad, S and Terasaki, PI and Murase, N and Kendall, RS and Kocova, M and Rudert, WA and Zeevi, A and Van Thiel, D (1993) Chimerism after Liver Transplantation for Type IV Glycogen Storage Disease and Type 1 Gaucher's Disease. New England Journal of Medicine, 328 (11). 745 - 749. ISSN 0028-4793

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Abstract

Background: Liver transplantation for type IV glycogen storage disease (branching-enzyme deficiency) results in the resorption of extrahepatic deposits of amylopectin, but the mechanism of resorption is not known. Methods: We studied two patients with type IV glycogen storage disease 37 and 91 months after liver transplantation and a third patient with lysosomal glucocerebrosidase deficiency (type 1 Gaucher's disease), in whom tissue glucocerebroside deposition had decreased 26 months after liver replacement, to determine whether the migration of cells from the allograft (microchimerism) could explain the improved metabolism of enzyme-deficient tissues in the recipient. Samples of blood and biopsy specimens of the skin, lymph nodes, heart, bone marrow, or intestine were examined immunocytochemically with the use of donor-specific monoclonal anti-HLA antibodies and the polymerase chain reaction, with preliminary amplification specific to donor alleles of the gene for the beta chain of HLA-DR molecules, followed by hybridization with allele-specific oligonucleotide probes. Results: Histopathological examination revealed that the cardiac deposits of amylopectin in the patients with glycogen storage disease and the lymph-node deposits of glucocerebroside in the patient with Gaucher's disease were dramatically reduced after transplantation. Immunocytochemical analysis showed cells containing the HLA phenotypes of the donor in the heart and skin of the patients with glycogen storage disease and in the lymph nodes, but not the skin, of the patient with Gaucher's disease. Polymerase-chain-reaction analysis demonstrated donor HLA-DR DNA in the heart of both patients with glycogen storage disease, in the skin of one of them, and in the skin, intestine, blood, and bone marrow of the patient with Gaucher's disease. Conclusions: Systemic microchimerism occurs after liver allotransplantation and can ameliorate pancellular enzyme deficiencies., In patients with type IV glycogen storage disease, deficiency of the branching enzyme α-1,4-glucan:α-1,4-glucan 6-glucosyltransferase is responsible for the accumulation in the liver and elsewhere of an insoluble and irritating amylopectin-like polysaccharide 1 . We recently described the absorption of this amylopectin from the extrahepatic tissues after liver transplantation, 2 leading Howell to predict that an explanation of the benefit would “clearly teach us a great deal about transplantation” 3 . That prediction has been shown to be accurate by our observation in this study that patients with type IV glycogen storage disease in whom liver transplantation was successful became chimeras: the cells… © 1993, Massachusetts Medical Society. All rights reserved.


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Details

Item Type: Article
Status: Published
Creators/Authors:
CreatorsEmailPitt UsernameORCID
Starzl, TEtes11@pitt.eduTES11
Demetris, AJ
Trucco, M
Ricordi, C
Ildstad, S
Terasaki, PI
Murase, N
Kendall, RS
Kocova, M
Rudert, WA
Zeevi, A
Van Thiel, D
Centers: Other Centers, Institutes, or Units > Thomas E. Starzl Transplantation Institute
Date: 18 March 1993
Date Type: Publication
Journal or Publication Title: New England Journal of Medicine
Volume: 328
Number: 11
Page Range: 745 - 749
DOI or Unique Handle: 10.1056/nejm199303183281101
Institution: University of Pittsburgh
Refereed: Yes
ISSN: 0028-4793
Other ID: uls-drl:31735062111996, Starzl CV No. 1407
Date Deposited: 08 Apr 2010 17:23
Last Modified: 13 Oct 2017 22:59
URI: http://d-scholarship.pitt.edu/id/eprint/4793

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