title: Outcome of children treated with haematopoietic-stem cell transplantations from donors expressing the rare C77G variant of the PTPRC (CD45) gene.
abstract: The uncommon C77G polymorphism of the Protein-Tyrosine Phosphatase (PTPRC) gene (PTPRC; previously termed CD45) could confer an increased risk of immunopathology. This study compared the outcome of children following human leucocyte antigen-matched unrelated haematopoïetic-stem cell transplantations (HSCT) from donors carrying (C77G cases: n = 8) or not (controls: n = 36) the PTPRC C77G polymorphism. Transmission of the PTPRC C77G polymorphism through the graft was suggested by unusual CD45RA phenotype in the donors and/or in the recipients after, but not before HSCT. Restriction-Fragment Length Polymorphism and sequencing confirmed the polymorphism. Overall survival rates were similar in C77G cases and controls (63% vs. 61%). Acute leukaemia relapse tended to be less frequent in C77G cases (0% vs. 32%; P = 0·09). Among recipients surviving ≥ 30 d, acute GVHD (aGVHD) ≥ grade 2 tended to be more frequent (100% vs. 58%; P = 0·07) and the rate of steroid-refractory or -dependant aGVHD higher (67% vs. 28%) in C77G cases. Finally, extensive chronic GVHD tended to occur more frequently (40% vs. 9%) in C77G cases. Recovery of lymphocyte subsets and virus-specific CD4 was similar in C77G cases and controls while interleukin 2 (IL2)-responses through CD3 stimulation were higher in C77G cases (P = 0·004). In conclusion, HSCT from PTPRC C77G donors could increase GVHD risk without compromising overall survival. Altered IL2-responses could be involved in this process.
authors.affiliation: Laboratory of Immunology, Robert Debré Hospital, Paris, France.
authors.forename: Samaan
authors.initials: S
authors.lastname: Samaan
authors.forename: Valérie
authors.initials: V
authors.lastname: Guérin-El Khourouj
authors.forename: Didier
authors.initials: D
authors.lastname: Auboeuf
authors.forename: Lucas
authors.initials: L
authors.lastname: Peltier
authors.forename: Béatrice
authors.initials: B
authors.lastname: Pédron
authors.forename: Marie
authors.initials: M
authors.lastname: Ouachée-Chardin
authors.forename: Nadége
authors.initials: N
authors.lastname: Gourgouillon
authors.forename: André
authors.initials: A
authors.lastname: Baruchel
authors.forename: Jean-Hugues
authors.initials: JH
authors.lastname: Dalle
authors.forename: Ghislaine
authors.initials: G
authors.lastname: Sterkers
mesh_terms: D000293:Adolescent; D015496:CD4-Positive T-Lymphocytes / Q000276:immunology; D016022:Case-Control Studies; D002478:Cells, Cultured; D002648:Child; D002675:Child, Preschool; D005260:Female; D005838:Genotype; D006084:Graft Rejection / Q000235:genetics / Q000276:immunology; D006086:Graft vs Host Disease / Q000235:genetics / Q000276:immunology; D018380:Hematopoietic Stem Cell Transplantation; D006801:Humans; D016130:Immunophenotyping; D007223:Infant; D007938:Leukemia / Q000628:therapy*; D017493:Leukocyte Common Antigens / Q000235:genetics* / Q000378:metabolism; D008297:Male; D010835:Phytohemagglutinins / Q000276:immunology; D012150:Polymorphism, Restriction Fragment Length; D014019:Tissue Donors; D016896:Treatment Outcome
chemical_list: D010835:Phytohemagglutinins; D017493:Leukocyte Common Antigens; C516769:PTPRC protein, human