Postnatal thymus transplantation with immunosuppression as treatment for DiGeorge syndrome

M. Louise Markert, Marilyn J. Alexieff, Jie Li, Marcelle Sarzotti, Daniel A. Ozaki, Blythe H. Devlin, Debra A. Sedlak, Gregory D. Sempowski, Laura P. Hale, Henry E. Rice, Samuel M. Mahaffey, Michael A. Skinner

Research output: Contribution to journalArticle

69 Scopus citations

Abstract

Complete DiGeorge syndrome is a fatal congenital disorder characterized by athymia, hypoparathyroidism, and heart defects. Less than half of patients are 22q11 hemizygous. The goal of this study was to assess if immune suppression followed by postnatal thymus transplantation would lead to T-cell function in 6 infant patients who had host T cells at the time of transplantation. All infants had fewer than 50 recent thymic emigrants (CD3+CD45RA +CD62L+) per cubic millimeter (mm3) and all had some proliferative response to the mitogen phytohemagglutinin. Four infants had rash, lymphadenopathy, and oligoclonal populations of T cells in the periphery. Five of 6 patients are alive at the follow-up interval of 15 months to 30 months. The 5 surviving patients developed a mean of 983 host CD3+ T cells/ mm3 (range, 536/mm3-1574/mm3), a mean of 437 recent thymic emigrants/mm3 (range, 196/mm3-785/ mm3), and normal proliferative responses to phytohemaglutinin (follow-up from day 376 to day 873). The TCR repertoire became polyclonal in patients who presented with oligoclonal T cells. All patients had thymopoiesis on allograft biopsy. Postnatal thymus transplantation after treatment with Thymoglobulin shows promise as therapy for infants with complete DiGeorge syndrome who have significant proliferative responses to mitogens or who develop rash, lymphadenopathy, and oligoclonal T cells.

Original languageEnglish (US)
Pages (from-to)2574-2581
Number of pages8
JournalBlood
Volume104
Issue number8
DOIs
StatePublished - Oct 15 2004

ASJC Scopus subject areas

  • Biochemistry
  • Immunology
  • Hematology
  • Cell Biology

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    Markert, M. L., Alexieff, M. J., Li, J., Sarzotti, M., Ozaki, D. A., Devlin, B. H., Sedlak, D. A., Sempowski, G. D., Hale, L. P., Rice, H. E., Mahaffey, S. M., & Skinner, M. A. (2004). Postnatal thymus transplantation with immunosuppression as treatment for DiGeorge syndrome. Blood, 104(8), 2574-2581. https://doi.org/10.1182/blood-2003-08-2984