Transplantation of thymus tissue in complete DiGeorge syndrome.

Published

Journal Article

BACKGROUND: The DiGeorge syndrome is a congenital disorder that affects the heart, parathyroid glands, and thymus. In complete DiGeorge syndrome, patients have severely reduced T-cell function. METHODS: We treated five infants (age, one to four months) with complete DiGeorge syndrome by transplantation of cultured postnatal thymus tissue. Follow-up evaluations included immune phenotyping and proliferative studies of peripheral-blood mononuclear cells plus biopsy of the thymus allograft. Thymic production of new T cells was assessed in peripheral blood by tests for T-cell-receptor recombination excision circles, which are formed from excised DNA during the rearrangement of T-cell-receptor genes. RESULTS: After the transplantation of thymus tissue, T-cell proliferative responses to mitogens developed in four of the five patients. Two of the patients survived with restoration of immune function; three patients died from infection or abnormalities unrelated to transplantation. Biopsies of grafted thymus in the surviving patients showed normal morphologic features and active T-cell production. In three patients, donor T cells could be detected about four weeks after transplantation, although there was no evidence of graft-versus-host disease on biopsy or at autopsy. In one patient, the T-cell development within the graft was demonstrated to accompany the appearance of recently developed T cells in the periphery and coincided with the onset of normal T-cell function. In one patient, there was evidence of thymus function and CD45RA+CD62L+ T cells more than five years after transplantation. CONCLUSIONS: In some infants with profound immunodeficiency and complete DiGeorge syndrome, the transplantation of thymus tissue can restore normal immune function. Early thymus transplantation - before the development of infectious complications - may promote successful immune reconstitution.

Full Text

Duke Authors

Cited Authors

  • Markert, ML; Boeck, A; Hale, LP; Kloster, AL; McLaughlin, TM; Batchvarova, MN; Douek, DC; Koup, RA; Kostyu, DD; Ward, FE; Rice, HE; Mahaffey, SM; Schiff, SE; Buckley, RH; Haynes, BF

Published Date

  • October 1999

Published In

Volume / Issue

  • 341 / 16

Start / End Page

  • 1180 - 1189

PubMed ID

  • 10523153

Pubmed Central ID

  • 10523153

Electronic International Standard Serial Number (EISSN)

  • 1533-4406

International Standard Serial Number (ISSN)

  • 0028-4793

Digital Object Identifier (DOI)

  • 10.1056/nejm199910143411603

Language

  • eng