title: Human leucocyte antigen-identical haematopoietic stem cell transplantation in major histocompatiblity complex class II immunodeficiency: reduced survival correlates with an increased incidence of acute graft-versus-host disease and pre-existing viral infections.
abstract: Major histocompatibility complex class II deficiency, a rare autosomal recessive primary immunodeficiency, is caused by the defective expression of human leucocyte antigen (HLA) class II molecules due to mutated trans-acting elements of any one of four regulatory genes (CIITA, RFXANK, RFX5, RFXAP). The impaired CD4 T-cell differentiation and antigen presentation in the periphery results in a severe defect of cellular and humoral response consistent with severe recurrent infections, leading to a poor prognosis. Currently, allogeneic haematopoietic stem cell transplantation (HSCT) is the only curative approach, but the overall cure rate is lower than in other immunodeficiencies. We report a single centre experience of 17 HSCTs with 15 HLA-identical donors between 1981 and 2004. Eight patients survived, while the occurrence of acute graft-versus-host disease (GVHD) was 50%. This study aimed to identify potential risk factors for GVHD and outcome within pre-HSCT complications related to the immunodeficiency. Five of seven patients with pre-existing viral infections developed acute GVHD > or = grade II, of whom four died. Two of seven patients without detectable pre-existing viral infection developed GVHD > or = grade II, and one died. The difference was significant (P < 0.05). A plausible link with other factors potentially associated with the development of GVHD could not be found. We suggest that the reduced survival after HLA-identical HSCT may be caused by the high incidence of pre-existing viral infections and associated with the onset of severe acute GVHD.
authors.affiliation: Unité d'Immunologie et Hématologie Pédiatrique, Faculté de Médecine Université Réné Descartes, Paris, France.
authors.forename: Raffaele
authors.initials: R
authors.lastname: Renella
authors.forename: Capucine
authors.initials: C
authors.lastname: Picard
authors.forename: Bénédicte
authors.initials: B
authors.lastname: Neven
authors.forename: Marie
authors.initials: M
authors.lastname: Ouachée-Chardin
authors.forename: Jean-Laurent
authors.initials: JL
authors.lastname: Casanova
authors.forename: Françoise
authors.initials: F
authors.lastname: Le Deist
authors.forename: Marina
authors.initials: M
authors.lastname: Cavazzana-Calvo
authors.forename: Stéphane
authors.initials: S
authors.lastname: Blanche
authors.forename: Alain
authors.initials: A
authors.lastname: Fischer
mesh_terms: D000208:Acute Disease; D002675:Child, Preschool; D016572:Cyclosporine / Q000627:therapeutic use; D005260:Female; D005500:Follow-Up Studies; D005838:Genotype; D006086:Graft vs Host Disease; D018380:Hematopoietic Stem Cell Transplantation / Q000379:methods*; D000949:Histocompatibility Antigens Class II / Q000276:immunology*; D006801:Humans; D007153:Immunologic Deficiency Syndromes / Q000276:immunology / Q000401:mortality / Q000601:surgery*; D007166:Immunosuppressive Agents / Q000627:therapeutic use; D015994:Incidence; D007223:Infant; D008297:Male; D008727:Methotrexate / Q000627:therapeutic use; D012189:Retrospective Studies; D015996:Survival Rate; D019172:Transplantation Conditioning; D014185:Transplantation, Isogeneic; D016896:Treatment Outcome; D014777:Virus Diseases / Q000150:complications / Q000276:immunology*
chemical_list: D000949:Histocompatibility Antigens Class II; D007166:Immunosuppressive Agents; D016572:Cyclosporine; D008727:Methotrexate