Transplantation of thymus tissue in complete DiGeorge syndrome

Background The DiGeorge syndrome is a congenital disorder that affects the heart, parathyroid glands, and thymus. In complete DiGeorge syndrome, patie nts have severely reduced T-cell function. Methods We treated five infants (age, one to four months) with complete DiG eorge syndrome by transplantation of cultured postnatal thymus tissue. Foll ow-up evaluations included immune phenotyping and proliferative studies of peripheral-blood mononuclear cells plus biopsy of the thymus allograft. Thy mic production of new T cells was assessed in peripheral blood by tests for T-cell-receptor recombination excision circles, which are formed from exci sed DNA during the rearrangement of T-cell-receptor genes. Results After the transplantation of thymus tissue, T-cell proliferative re sponses to mitogens developed in four of the five patients. Two of the pati ents survived with restoration of immune function; three patients died from infection or abnormalities unrelated to transplantation. Biopsies of graft ed thymus in the surviving patients showed normal morphologic features and active T-cell production. In three patients, donor T cells could be detecte d 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-c ell development within the graft was demonstrated to accompany the appearan ce of recently developed T cells in the periphery and coincided with the on set of normal T-cell function. In one patient, there was evidence of thymus function and CD45RA+CD62L+ T cells more than five years after transplantat ion. Conclusions In some infants with profound immunodeficiency and complete DiG eorge syndrome, the transplantation of thymus tissue can restore normal imm une function. Early thymus transplantation - before the development of infe ctious complications - may promote successful immune reconstitution. (N Eng l J Med 1999;341:1180-9.) (C)1999, Massachusetts Medical Society.