title: Postnatal thymus transplantation with immunosuppression as treatment for DiGeorge syndrome.
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 (mm(3)) 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/mm(3) (range, 536/mm(3)-1574/mm(3)), a mean of 437 recent thymic emigrants/mm(3) (range, 196/mm(3)-785/mm(3)), 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.
authors.affiliation: Department of Pediatrics, Human Vaccine Institute, Duke University Medical Center, Durham, NC 27710, USA. marke001@mc.duke.edu
authors.forename: M Louise
authors.initials: ML
authors.lastname: Markert
authors.forename: Marilyn J
authors.initials: MJ
authors.lastname: Alexieff
authors.forename: Jie
authors.initials: J
authors.lastname: Li
authors.forename: Marcella
authors.initials: M
authors.lastname: Sarzotti
authors.forename: Daniel A
authors.initials: DA
authors.lastname: Ozaki
authors.forename: Blythe H
authors.initials: BH
authors.lastname: Devlin
authors.forename: Debra A
authors.initials: DA
authors.lastname: Sedlak
authors.forename: Gregory D
authors.initials: GD
authors.lastname: Sempowski
authors.forename: Laura P
authors.initials: LP
authors.lastname: Hale
authors.forename: Henry E
authors.initials: HE
authors.lastname: Rice
authors.forename: Samuel M
authors.initials: SM
authors.lastname: Mahaffey
authors.forename: Michael A
authors.initials: MA
authors.lastname: Skinner
mesh_terms: D004062:DiGeorge Syndrome / Q000276:immunology* / Q000473:pathology / Q000601:surgery / Q000628:therapy*; D006650:Histocompatibility Testing; D006801:Humans; D007165:Immunosuppression Therapy; D007223:Infant; D015996:Survival Rate; D013950:Thymus Gland / Q000276:immunology* / Q000637:transplantation*; D016896:Treatment Outcome