title: T-cell immune constitution after peripheral blood mononuclear cell transplantation in complete DiGeorge syndrome.
abstract: Complete DiGeorge syndrome (cDGS) is a congenital disorder characterized by typical facies, thymic aplasia, susceptibility to infections, hypoparathyroidism and conotruncal cardiac defect. Fetal thymus or post-natal thymus tissue transplantations and human leucocyte antigen (HLA)-genoidentical bone marrow transplantations were followed in a few cases by immune reconstitution. More recently, a peripheral blood mononuclear cell transplantation (PBMCT) was performed with an HLA-genoidentical donor and followed by a partial T-cell engraftment and immune reconstitution. We report a boy with cDGS, without cardiac defect, who suffered recurrent severe infections. At the age of 4 years, he underwent PBMCT from his HLA-genoidentical sister. He received no conditioning regimen, but graft-versus-host disease (GVHD) prophylaxis was with oral cyclosporin A and mycophenolate mofetil. Toxicity was mild, with grade I acute GVHD. The patient is currently 2.5 years post-PBMCT with excellent clinical performances. Mixed chimaerism can only be observed on the T-cell population (50% donor T cells). T-lymphocyte count fluctuated (CD3 more than 400 x 10(6)/l at d 84 and CD4 more than 200 x 10(6)/l at d 46). Exclusive memory phenotype T cells and absence of new thymic emigrants suggest expansion of infused T cells. T-cell mitogen and tetanus antigen responses normalized a few months after transplantation. After immunizations, specific antibodies were produced. PBMCT from an HLA identical sibling could be an efficient treatment of immune deficiency in cDGS.
authors.affiliation: Unité de Thérapie cellulaire et Tissus, CHU de Nancy, UMR CNRS 7563, Allée du Morvan, 54511 Vandoeuvre-lès-Nancy, France. d.bensoussan@chu-nancy.fr
authors.forename: Danièle
authors.initials: D
authors.lastname: Bensoussan
authors.forename: Françoise
authors.initials: F
authors.lastname: Le Deist
authors.forename: Véronique
authors.initials: V
authors.lastname: Latger-Cannard
authors.forename: Marie José
authors.initials: MJ
authors.lastname: Grégoire
authors.forename: Odile
authors.initials: O
authors.lastname: Avinens
authors.forename: Pierre
authors.initials: P
authors.lastname: Feugier
authors.forename: Violaine
authors.initials: V
authors.lastname: Bourdon
authors.forename: Christine
authors.initials: C
authors.lastname: André-Botté
authors.forename: Claudine
authors.initials: C
authors.lastname: Schmitt
authors.forename: Philippe
authors.initials: P
authors.lastname: Jonveaux
authors.forename: Jean François
authors.initials: JF
authors.lastname: Eliaou
authors.forename: Jean François
authors.initials: JF
authors.lastname: Stoltz
authors.forename: Pierre
authors.initials: P
authors.lastname: Bordigoni
mesh_terms: D000208:Acute Disease; D015496:CD4-Positive T-Lymphocytes / Q000276:immunology; D018414:CD8-Positive T-Lymphocytes / Q000276:immunology; D004062:DiGeorge Syndrome / Q000276:immunology* / Q000601:surgery*; D006086:Graft vs Host Disease / Q000276:immunology; D006801:Humans; D007114:Immunization; D007231:Infant, Newborn; D007963:Leukocytes, Mononuclear / Q000637:transplantation*; D018655:Lymphocyte Count; D008297:Male; D011110:Polymorphism, Genetic; D011184:Postoperative Period; D013601:T-Lymphocytes / Q000276:immunology*; D018183:Transplantation Chimera; D014185:Transplantation, Isogeneic