title: CD45RA depletion in HLA-mismatched allogeneic hematopoietic stem cell transplantation for primary combined immunodeficiency: A preliminary study.
abstract: BACKGROUND
  Combined immunodeficiencies (CIDs) form a heterogeneous group of inherited conditions that affect the development, function, or both of T cells. The treatment of CIDs with allogeneic hematopoietic stem cell transplantation (HSCT) is complicated by a high incidence of life-threatening infections and an increased risk of graft-versus-host disease (GVHD).
  
  
  OBJECTIVE
  In view of the growing evidence that alloreactivity is mainly derived from human naive T cells, the selective depletion of naive T cells from allografts might constitute a way of reducing alloreactivity while maintaining memory T-cell responsiveness to pathogens.
  
  
  METHODS
  Five consecutive patients with CIDs and chronic viral infections underwent an allogeneic, HLA-mismatched HSCT. Given the patients' infection status and the potential risk of severe GVHD in the mismatched setting, the CD34(-) fraction of the allograft was depleted of naive T cells by using magnetic CD45RA beads.
  
  
  RESULTS
  Engraftment occurred in 4 of the 5 patients. No severe GVHD occurred. In the 4 engrafted patients viral infections were cleared within 2 months of the HSCT, and both cellular and humoral immunity were re-established within a year of the HSCT. An early T-cell response against viral pathogens was documented in 2 patients.
  
  
  CONCLUSIONS
  The present pilot study shows that clinical-grade depletion of naive T cells from an allograft through the use of magnetic CD45RA beads seems to be a feasible and efficacious option for the treatment of patients with CIDs at high risk of GVHD, infection, or both in an HLA-mismatched setting.
authors.affiliation: Département de Biothérapie, Centre d'Investigation Clinique intégré en Biothérapies, Hôpital Necker-Enfants Malades, Assistance Publique-Hôpitaux de Paris (AP-HP), Paris, France; Université Paris Descartes-Sorbonne Paris Cité, Institut Imagine, Paris, France; INSERM UMR1163, Paris, France. Electronic address: fabien.touzot@nck.aphp.fr.
authors.forename: Fabien
authors.initials: F
authors.lastname: Touzot
authors.affiliation: Université Paris Descartes-Sorbonne Paris Cité, Institut Imagine, Paris, France; Unité d'Immunologie-Hématologie et Rhumatologie Pédiatrique, Hôpital Necker-Enfants Malades, AP-HP, Paris, France; INSERM UMR1163, Paris, France.
authors.forename: Bénédicte
authors.initials: B
authors.lastname: Neven
authors.affiliation: Département de Biothérapie, Centre d'Investigation Clinique intégré en Biothérapies, Hôpital Necker-Enfants Malades, Assistance Publique-Hôpitaux de Paris (AP-HP), Paris, France.
authors.forename: Liliane
authors.initials: L
authors.lastname: Dal-Cortivo
authors.affiliation: Département de Biothérapie, Centre d'Investigation Clinique intégré en Biothérapies, Hôpital Necker-Enfants Malades, Assistance Publique-Hôpitaux de Paris (AP-HP), Paris, France.
authors.forename: Aurélie
authors.initials: A
authors.lastname: Gabrion
authors.affiliation: Université Paris Descartes-Sorbonne Paris Cité, Institut Imagine, Paris, France; Unité d'Immunologie-Hématologie et Rhumatologie Pédiatrique, Hôpital Necker-Enfants Malades, AP-HP, Paris, France; INSERM UMR1163, Paris, France.
authors.forename: Despina
authors.initials: D
authors.lastname: Moshous
authors.affiliation: Université Paris Descartes-Sorbonne Paris Cité, Institut Imagine, Paris, France; Unité d'Immunologie-Hématologie et Rhumatologie Pédiatrique, Hôpital Necker-Enfants Malades, AP-HP, Paris, France.
authors.forename: Guilhem
authors.initials: G
authors.lastname: Cros
authors.affiliation: Université Paris Descartes-Sorbonne Paris Cité, Institut Imagine, Paris, France; Unité d'Immunologie-Hématologie et Rhumatologie Pédiatrique, Hôpital Necker-Enfants Malades, AP-HP, Paris, France.
authors.forename: Maryline
authors.initials: M
authors.lastname: Chomton
authors.affiliation: Département de Biothérapie, Centre d'Investigation Clinique intégré en Biothérapies, Hôpital Necker-Enfants Malades, Assistance Publique-Hôpitaux de Paris (AP-HP), Paris, France.
authors.forename: Jean-Marc
authors.initials: JM
authors.lastname: Luby
authors.affiliation: Département de Biothérapie, Centre d'Investigation Clinique intégré en Biothérapies, Hôpital Necker-Enfants Malades, Assistance Publique-Hôpitaux de Paris (AP-HP), Paris, France.
authors.forename: Brigitte
authors.initials: B
authors.lastname: Terniaux
authors.affiliation: Département de Biothérapie, Centre d'Investigation Clinique intégré en Biothérapies, Hôpital Necker-Enfants Malades, Assistance Publique-Hôpitaux de Paris (AP-HP), Paris, France; Université Paris Descartes-Sorbonne Paris Cité, Institut Imagine, Paris, France.
authors.forename: Jérémy
authors.initials: J
authors.lastname: Magalon
authors.affiliation: Université Paris Descartes-Sorbonne Paris Cité, Institut Imagine, Paris, France; Centre d'étude des déficits immunitaires (CEDI), Hôpital Necker-Enfants Malades, AP-HP, Paris, France; INSERM UMR1163, Paris, France.
authors.forename: Capucine
authors.initials: C
authors.lastname: Picard
authors.affiliation: Université Paris Descartes-Sorbonne Paris Cité, Institut Imagine, Paris, France; Unité d'Immunologie-Hématologie et Rhumatologie Pédiatrique, Hôpital Necker-Enfants Malades, AP-HP, Paris, France.
authors.forename: Stéphane
authors.initials: S
authors.lastname: Blanche
authors.affiliation: Université Paris Descartes-Sorbonne Paris Cité, Institut Imagine, Paris, France; Unité d'Immunologie-Hématologie et Rhumatologie Pédiatrique, Hôpital Necker-Enfants Malades, AP-HP, Paris, France; INSERM UMR1163, Paris, France; College de France, Paris, France.
authors.forename: Alain
authors.initials: A
authors.lastname: Fischer
authors.affiliation: Département de Biothérapie, Centre d'Investigation Clinique intégré en Biothérapies, Hôpital Necker-Enfants Malades, Assistance Publique-Hôpitaux de Paris (AP-HP), Paris, France; Université Paris Descartes-Sorbonne Paris Cité, Institut Imagine, Paris, France; INSERM UMR1163, Paris, France.
authors.forename: Marina
authors.initials: M
authors.lastname: Cavazzana
mesh_terms: D002675:Child, Preschool; D005500:Follow-Up Studies; D006085:Graft Survival / Q000276:immunology; D006086:Graft vs Host Disease / Q000209:etiology / Q000517:prevention & control; D006680:HLA Antigens / Q000276:immunology*; D018380:Hematopoietic Stem Cell Transplantation / Q000009:adverse effects; D006801:Humans; D007070:Immunoglobulin A / Q000276:immunology; D007074:Immunoglobulin G / Q000276:immunology; D007075:Immunoglobulin M / Q000276:immunology; D007153:Immunologic Deficiency Syndromes / Q000175:diagnosis / Q000276:immunology* / Q000378:metabolism / Q000628:therapy*; D007223:Infant; D017493:Leukocyte Common Antigens / Q000378:metabolism; D008212:Lymphocyte Depletion; D016176:T-Lymphocyte Subsets / Q000276:immunology / Q000378:metabolism; D019172:Transplantation Conditioning; D014184:Transplantation, Homologous; D016896:Treatment Outcome
chemical_list: D006680:HLA Antigens; D007070:Immunoglobulin A; D007074:Immunoglobulin G; D007075:Immunoglobulin M; D017493:Leukocyte Common Antigens
keywords: Combined primary immunodeficiency; graft-versus-host disease; hematopoietic stem cell transplantation; immunomagnetic CD45RA depletion; naive T cell; viral infection