TY - JOUR
T1 - Postnatal thymus transplantation with immunosuppression as treatment for DiGeorge syndrome
AU - Markert, M. Louise
AU - Alexieff, Marilyn J.
AU - Li, Jie
AU - Sarzotti, Marcelle
AU - Ozaki, Daniel A.
AU - Devlin, Blythe H.
AU - Sedlak, Debra A.
AU - Sempowski, Gregory D.
AU - Hale, Laura P.
AU - Rice, Henry E.
AU - Mahaffey, Samuel M.
AU - Skinner, Michael A.
PY - 2004/10/15
Y1 - 2004/10/15
N2 - 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.
AB - 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.
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U2 - 10.1182/blood-2003-08-2984
DO - 10.1182/blood-2003-08-2984
M3 - Article
C2 - 15100156
AN - SCOPUS:1942538141
SN - 0006-4971
VL - 104
SP - 2574
EP - 2581
JO - Blood
JF - Blood
IS - 8
ER -