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Transplantation of thymus tissue in complete DiGeorge syndrome
M L Markert1, A Boeck, L P Hale
1Department of Pediatrics, Duke Comprehensive Cancer Center, Duke University Medical Center, Durham, NC 27710, USA. marke001@mc.duke.edu
Insights
Thymus tissue transplantation can restore immune function in infants with complete DiGeorge syndrome. Early intervention is key for successful immune reconstitution and T-cell development.
Area of Science:
- Immunology
- Developmental Biology
- Transplantation Medicine
Background:
- DiGeorge syndrome is a congenital disorder impacting the heart, parathyroid glands, and thymus.
- Complete DiGeorge syndrome is characterized by severely impaired T-cell function.
Purpose of the Study:
- To evaluate the efficacy of cultured postnatal thymus tissue transplantation in infants with complete DiGeorge syndrome.
- To assess immune reconstitution and T-cell production following thymus transplantation.
Main Methods:
- Five infants with complete DiGeorge syndrome received thymus tissue transplants.
- Immune phenotyping, T-cell proliferation studies, and thymus allograft biopsies were performed.
- T-cell production was monitored using T-cell-receptor recombination excision circles.
Main Results:
- Four of five patients showed restored T-cell proliferative responses post-transplantation.
- Two patients achieved immune reconstitution; three died from unrelated complications.
- Surviving patients exhibited normal thymus morphology and active T-cell production, with donor T cells detected for up to five years.
Conclusions:
- Thymus tissue transplantation can restore immune function in infants with profound immunodeficiency due to DiGeorge syndrome.
- Early thymus transplantation, prior to infectious complications, may significantly improve outcomes and immune reconstitution.
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.