title: Thymus transplantation for complete DiGeorge syndrome: European experience.
abstract: BACKGROUND
  Thymus transplantation is a promising strategy for the treatment of athymic complete DiGeorge syndrome (cDGS).
  
  
  METHODS
  Twelve patients with cDGS underwent transplantation with allogeneic cultured thymus.
  
  
  OBJECTIVE
  We sought to confirm and extend the results previously obtained in a single center.
  
  
  RESULTS
  Two patients died of pre-existing viral infections without having thymopoiesis, and 1 late death occurred from autoimmune thrombocytopenia. One infant had septic shock shortly after transplantation, resulting in graft loss and the need for a second transplant. Evidence of thymopoiesis developed from 5 to 6 months after transplantation in 10 patients. Median circulating naive CD4 counts were 44 × 106/L (range, 11-440 × 106/L) and 200 × 106/L (range, 5-310 × 106/L) at 12 and 24 months after transplantation and T-cell receptor excision circles were 2,238/106T cells (range, 320-8,807/106T cells) and 4,184/106T cells (range, 1,582-24,596/106T cells). Counts did not usually reach normal levels for age, but patients were able to clear pre-existing infections and those acquired later. At a median of 49 months (range, 22-80 months), 8 have ceased prophylactic antimicrobials, and 5 have ceased immunoglobulin replacement. Histologic confirmation of thymopoiesis was seen in 7 of 11 patients undergoing biopsy of transplanted tissue, including 5 showing full maturation through to the terminal stage of Hassall body formation. Autoimmune regulator expression was also demonstrated. Autoimmune complications were seen in 7 of 12 patients. In 2 patients early transient autoimmune hemolysis settled after treatment and did not recur. The other 5 experienced ongoing autoimmune problems, including thyroiditis (3), hemolysis (1), thrombocytopenia (4), and neutropenia (1).
  
  
  CONCLUSIONS
  This study confirms the previous reports that thymus transplantation can reconstitute T cells in patients with cDGS but with frequent autoimmune complications in survivors.
authors.affiliation: Infection, Immunity and Inflammation Theme, UCL Great Ormond Street Institute of Child Health, London, United Kingdom; Department of Immunology, Great Ormond Street Hospital, London, United Kingdom. Electronic address: Graham.Davies@gosh.nhs.uk.
authors.forename: E Graham
authors.initials: EG
authors.lastname: Davies
authors.affiliation: Infection, Immunity and Inflammation Theme, UCL Great Ormond Street Institute of Child Health, London, United Kingdom.
authors.forename: Melissa
authors.initials: M
authors.lastname: Cheung
authors.affiliation: Department of Immunology, Great Ormond Street Hospital, London, United Kingdom.
authors.forename: Kimberly
authors.initials: K
authors.lastname: Gilmour
authors.affiliation: Infection, Immunity and Inflammation Theme, UCL Great Ormond Street Institute of Child Health, London, United Kingdom.
authors.forename: Jesmeen
authors.initials: J
authors.lastname: Maimaris
authors.affiliation: Department of Immunology, Great Ormond Street Hospital, London, United Kingdom.
authors.forename: Joe
authors.initials: J
authors.lastname: Curry
authors.affiliation: Infection, Immunity and Inflammation Theme, UCL Great Ormond Street Institute of Child Health, London, United Kingdom; School of Life Sciences, University of Bedfordshire, Luton, United Kingdom.
authors.forename: Anna
authors.initials: A
authors.lastname: Furmanski
authors.affiliation: Department of Immunology, Great Ormond Street Hospital, London, United Kingdom.
authors.forename: Neil
authors.initials: N
authors.lastname: Sebire
authors.affiliation: Institute of Immunity and Transplantation, Division of Infection & Immunity, School of Life and Medical Sciences, Royal Free Hospital, University College London, London, United Kingdom.
authors.forename: Neil
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authors.lastname: Halliday
authors.affiliation: Infection, Immunity and Inflammation Theme, UCL Great Ormond Street Institute of Child Health, London, United Kingdom.
authors.forename: Konstantinos
authors.initials: K
authors.lastname: Mengrelis
authors.affiliation: Department of Immunology, Great Ormond Street Hospital, London, United Kingdom.
authors.forename: Stuart
authors.initials: S
authors.lastname: Adams
authors.affiliation: Department of Paediatric Immunology and Infectious Diseases, Bristol Children's Hospital, Bristol, United Kingdom.
authors.forename: Jolanta
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authors.lastname: Bernatoniene
authors.affiliation: Department of Gastroenterology, Birmingham Children's Hospital, Birmingham, United Kingdom.
authors.forename: Ronald
authors.initials: R
authors.lastname: Bremner
authors.affiliation: Department of Immunology, Leicester Royal Infirmary, Leicester, United Kingdom.
authors.forename: Michael
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authors.lastname: Browning
authors.affiliation: Division of Allergy and Immunology, Department of Pediatrics, Duke University Medical Center, Durham, NC.
authors.forename: Blythe
authors.initials: B
authors.lastname: Devlin
authors.affiliation: Division of Paediatric and Adolescent Medicine, Section of Paediatric Medicine and Transplantation, Oslo University Hospital, Oslo, Norway.
authors.forename: Hans Christian
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authors.affiliation: Infection, Immunity and Inflammation Theme, UCL Great Ormond Street Institute of Child Health, London, United Kingdom; Department of Immunology, Great Ormond Street Hospital, London, United Kingdom.
authors.forename: H Bobby
authors.initials: HB
authors.lastname: Gaspar
authors.affiliation: Department of Paediatric Immunology and Infectious Diseases, Bristol Children's Hospital, Bristol, United Kingdom.
authors.forename: Lizzie
authors.initials: L
authors.lastname: Hutchison
authors.affiliation: Infection, Immunity and Inflammation Theme, UCL Great Ormond Street Institute of Child Health, London, United Kingdom; Department of Immunology, Great Ormond Street Hospital, London, United Kingdom.
authors.forename: Winnie
authors.initials: W
authors.lastname: Ip
authors.affiliation: Paediatric Clinic II, Copenhagen University Hospital, Rigshospitalet, Copenhagen, Denmark.
authors.forename: Marianne
authors.initials: M
authors.lastname: Ifversen
authors.affiliation: Department of Paediatric Immunology and Infectious Diseases, Our Lady's Children's Hospital, Crumlin, Dublin, Ireland.
authors.forename: T Ronan
authors.initials: TR
authors.lastname: Leahy
authors.affiliation: Division of Allergy and Immunology, Department of Pediatrics, Duke University Medical Center, Durham, NC.
authors.forename: Elizabeth
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authors.lastname: McCarthy
authors.affiliation: Paediatric Immunology, Haematology and Rheumatology Unit, Hopital Necker, Paris, France.
authors.forename: Despina
authors.initials: D
authors.lastname: Moshous
authors.affiliation: Department of Paediatrics, University Hospital, Coventry, United Kingdom.
authors.forename: Kim
authors.initials: K
authors.lastname: Neuling
authors.affiliation: Department of Immunology, Children's Memorial Health Institute, Warsaw, Poland.
authors.forename: Malgorzata
authors.initials: M
authors.lastname: Pac
authors.affiliation: Paediatric Clinic, Polyclinic Regina Maria Baneasa, Bucharest, Romania.
authors.forename: Alina
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authors.lastname: Papadopol
authors.affiliation: Infection, Immunity and Inflammation Theme, UCL Great Ormond Street Institute of Child Health, London, United Kingdom; Department of Immunology, Great Ormond Street Hospital, London, United Kingdom.
authors.forename: Kathryn L
authors.initials: KL
authors.lastname: Parsley
authors.affiliation: Institute of Immunity and Translational Medicine, University of Brescia, Brescia, Italy.
authors.forename: Luigi
authors.initials: L
authors.lastname: Poliani
authors.affiliation: Infection, Immunity and Inflammation Theme, UCL Great Ormond Street Institute of Child Health, London, United Kingdom.
authors.forename: Ida
authors.initials: I
authors.lastname: Ricciardelli
authors.affiliation: Institute of Immunity and Transplantation, Division of Infection & Immunity, School of Life and Medical Sciences, Royal Free Hospital, University College London, London, United Kingdom.
authors.forename: David M
authors.initials: DM
authors.lastname: Sansom
authors.affiliation: The Children's Clinic, Tartu University Hospital, Tartu, Estonia.
authors.forename: Tiia
authors.initials: T
authors.lastname: Voor
authors.affiliation: Infection, Immunity and Inflammation Theme, UCL Great Ormond Street Institute of Child Health, London, United Kingdom; Department of Immunology, Great Ormond Street Hospital, London, United Kingdom.
authors.forename: Austen
authors.initials: A
authors.lastname: Worth
authors.affiliation: Infection, Immunity and Inflammation Theme, UCL Great Ormond Street Institute of Child Health, London, United Kingdom.
authors.forename: Tessa
authors.initials: T
authors.lastname: Crompton
authors.affiliation: Department of Immunology, Leicester Royal Infirmary, Leicester, United Kingdom.
authors.forename: M Louise
authors.initials: ML
authors.lastname: Markert
authors.affiliation: Infection, Immunity and Inflammation Theme, UCL Great Ormond Street Institute of Child Health, London, United Kingdom.
authors.forename: Adrian J
authors.initials: AJ
authors.lastname: Thrasher
mesh_terms: D001327:Autoimmune Diseases / Q000209:etiology / Q000276:immunology*; D002478:Cells, Cultured; D002648:Child; D002675:Child, Preschool; D004062:DiGeorge Syndrome / Q000276:immunology / Q000628:therapy*; D005060:Europe; D005260:Female; D006801:Humans; D000074243:Immune Reconstitution; D007223:Infant; D008297:Male; D009924:Organ Culture Techniques; D016377:Organ Transplantation; D011183:Postoperative Complications / Q000276:immunology*; D013601:T-Lymphocytes / Q000276:immunology*; D013950:Thymus Gland / Q000637:transplantation*; D014184:Transplantation, Homologous; D016896:Treatment Outcome
keywords: DiGeorge syndrome; athymia; thymus transplantation