title: Host natural killer immunity is a key indicator of permissiveness for donor cell engraftment in patients with severe combined immunodeficiency.
abstract: BACKGROUND
  Severe combined immunodeficiency (SCID) can be cured by using allogeneic hematopoietic stem cell transplantation, and the absence of host immunity often obviates the need for preconditioning. Depending on the underlying genetic defect and when blocks in differentiation occur during lymphocyte ontogeny, infants with SCID have absent or greatly reduced numbers of functional T cells. Natural killer (NK) cell populations are usually absent in the SCID-X1 and Janus kinase 3 forms of SCID and greatly reduced in adenosine deaminase deficiency SCID but often present in other forms of the disorder.
  
  
  OBJECTIVE
  To determine if SCID phenotypes indicate host permissiveness to donor cell engraftment.
  
  
  METHODS
  A retrospective data analysis considered whether host NK cells influenced donor T-cell engraftment, immune reconstitution, and long-term outcomes in children who had undergone nonconditioned allogeneic stem cell transplantation between 1990 and 2011 in the United Kingdom. Detailed analysis of T- and B-cell immune reconstitution and donor chimerism was compared between the NK(+) (n = 24) and NK(-) (n = 53) forms of SCID.
  
  
  RESULTS
  Overall, 77 children underwent transplantation, with survival of 90% in matched sibling donor/matched family donor transplants compared with 60% when alternative donors were used. Infants with NK(-)SCID were more likely to survive than NK(+) recipients (87% vs 62%, P < .01) and had high-level donor T-cell chimerism with superior long-term recovery of CD4 T-cell immunity. Notably, 33% of children with NK(+)SCID required additional transplantation procedures compared with only 8% of children with NK(-)SCID (P < .005).
  
  
  CONCLUSIONS
  NK(-)SCID disorders are highly permissive for donor T-cell engraftment without preconditioning, whereas the presence of NK cells is a strong indicator that preparative conditioning is required for engraftment of T-cell precursors capable of supporting robust T-cell reconstitution.
authors.affiliation: Immunology and Bone Marrow Transplant Units, Great Ormond Street Hospital for Children, London, United Kingdom.
authors.forename: Amel
authors.initials: A
authors.lastname: Hassan
authors.affiliation: Cellular & Molecular Immunology, Institute of Child Health, University College London, London, United Kingdom.
authors.forename: Pamela
authors.initials: P
authors.lastname: Lee
authors.affiliation: Bone Marrow Transplant Unit, Great North Children's Hospital, Royal Victoria Infirmary, Newcastle upon Tyne, United Kingdom.
authors.forename: Paraskevi
authors.initials: P
authors.lastname: Maggina
authors.affiliation: Immunology and Bone Marrow Transplant Units, Great Ormond Street Hospital for Children, London, United Kingdom.
authors.forename: Jin Hua
authors.initials: JH
authors.lastname: Xu
authors.affiliation: Bone Marrow Transplant Unit, Great North Children's Hospital, Royal Victoria Infirmary, Newcastle upon Tyne, United Kingdom.
authors.forename: Diana
authors.initials: D
authors.lastname: Moreira
authors.affiliation: Institute of Cellular Medicine, University of Newcastle, Newcastle upon Tyne, United Kingdom.
authors.forename: Mary
authors.initials: M
authors.lastname: Slatter
authors.affiliation: Bone Marrow Transplant Unit, Great North Children's Hospital, Royal Victoria Infirmary, Newcastle upon Tyne, United Kingdom.
authors.forename: Zohreh
authors.initials: Z
authors.lastname: Nademi
authors.affiliation: Immunology and Bone Marrow Transplant Units, Great Ormond Street Hospital for Children, London, United Kingdom.
authors.forename: Austen
authors.initials: A
authors.lastname: Worth
authors.affiliation: Immunology and Bone Marrow Transplant Units, Great Ormond Street Hospital for Children, London, United Kingdom.
authors.forename: Stuart
authors.initials: S
authors.lastname: Adams
authors.affiliation: Immunology and Bone Marrow Transplant Units, Great Ormond Street Hospital for Children, London, United Kingdom.
authors.forename: Alison
authors.initials: A
authors.lastname: Jones
authors.affiliation: Immunology and Bone Marrow Transplant Units, Great Ormond Street Hospital for Children, London, United Kingdom.
authors.forename: Catherine
authors.initials: C
authors.lastname: Cale
authors.affiliation: Immunology and Bone Marrow Transplant Units, Great Ormond Street Hospital for Children, London, United Kingdom.
authors.forename: Zoe
authors.initials: Z
authors.lastname: Allwood
authors.affiliation: Immunology and Bone Marrow Transplant Units, Great Ormond Street Hospital for Children, London, United Kingdom.
authors.forename: Kanchan
authors.initials: K
authors.lastname: Rao
authors.affiliation: Immunology and Bone Marrow Transplant Units, Great Ormond Street Hospital for Children, London, United Kingdom.
authors.forename: Robert
authors.initials: R
authors.lastname: Chiesa
authors.affiliation: Cellular & Molecular Immunology, Institute of Child Health, University College London, London, United Kingdom.
authors.forename: Persis
authors.initials: P
authors.lastname: Amrolia
authors.affiliation: Cellular & Molecular Immunology, Institute of Child Health, University College London, London, United Kingdom.
authors.forename: Hubert
authors.initials: H
authors.lastname: Gaspar
authors.affiliation: Cellular & Molecular Immunology, Institute of Child Health, University College London, London, United Kingdom.
authors.forename: E Graham
authors.initials: EG
authors.lastname: Davies
authors.affiliation: Immunology and Bone Marrow Transplant Units, Great Ormond Street Hospital for Children, London, United Kingdom.
authors.forename: Paul
authors.initials: P
authors.lastname: Veys
authors.affiliation: Institute of Cellular Medicine, University of Newcastle, Newcastle upon Tyne, United Kingdom.
authors.forename: Andrew
authors.initials: A
authors.lastname: Gennery
authors.affiliation: Cellular & Molecular Immunology, Institute of Child Health, University College London, London, United Kingdom. Electronic address: W.Qasim@ucl.ac.uk.
authors.forename: Waseem
authors.initials: W
authors.lastname: Qasim
mesh_terms: D019070:Cell Lineage / Q000276:immunology; D005260:Female; D006085:Graft Survival / Q000276:immunology*; D018380:Hematopoietic Stem Cell Transplantation; D006801:Humans; D007223:Infant; D007231:Infant, Newborn; D007694:Killer Cells, Natural / Q000276:immunology*; D008297:Male; D016511:Severe Combined Immunodeficiency / Q000276:immunology* / Q000401:mortality / Q000628:therapy; D016176:T-Lymphocyte Subsets / Q000276:immunology / Q000378:metabolism; D018183:Transplantation Chimera; D019172:Transplantation Conditioning; D014184:Transplantation, Homologous
keywords: Severe combined immunodeficiency; adenosine deaminase deficiency; chimerism; conditioning; engraftment; natural killer cells