title: Recipient PTPN22 -1123 C/C genotype predicts acute graft-versus-host disease after HLA fully matched unrelated bone marrow transplantation for hematologic malignancies.
abstract: PTPN22 is a critical negative regulator of T cell responses. Its promoter gene variant (rs2488457, -1123G>C) has been reported to be associated with autoimmune diseases. This study analyzed the impact of the PTPN22 variant on transplantation outcomes in a cohort of 663 patients who underwent unrelated HLA-matched bone marrow transplantation (BMT) for hematologic malignancies through the Japan Marrow Donor Program. The recipient C/C genotype versus the recipient G/G genotype resulted in a lower incidence of grade II-IV acute graft-versus-host disease (hazard ratio [HR], 0.50; 95% confidence interval [CI], 0.29-0.85; P = .01), as well as a higher incidence of relapse (HR, 1.78; 95% CI, 1.10-2.90; P = .02), as demonstrated on multivariate analysis. In patients with high-risk disease, the recipient C/C genotype was associated with significantly worse overall survival rates than the recipient G/G genotype (HR, 1.60; 95% CI, 1.02-2.51; P = .04), whereas this effect was absent in patients with standard-risk disease. In addition, the donor G/C genotype was associated with a lower incidence of relapse (HR, 0.58; 95% CI, 0.40-0.85), which did not influence survival. Our findings suggest that PTPN22 genotyping could be useful in predicting prognoses and creating therapeutic strategies for improving the final outcomes of allogeneic BMT.
authors.affiliation: Department of Hematology and Oncology, Kanazawa University Hospital, Kanazawa, Japan.
authors.forename: J Luis
authors.initials: JL
authors.lastname: Espinoza
authors.forename: Akiyoshi
authors.initials: A
authors.lastname: Takami
authors.forename: Makoto
authors.initials: M
authors.lastname: Onizuka
authors.forename: Yasuo
authors.initials: Y
authors.lastname: Morishima
authors.forename: Takahiro
authors.initials: T
authors.lastname: Fukuda
authors.forename: Yoshihisa
authors.initials: Y
authors.lastname: Kodera
authors.forename: Hideki
authors.initials: H
authors.lastname: Akiyama
authors.forename: Koichi
authors.initials: K
authors.lastname: Miyamura
authors.forename: Takehiko
authors.initials: T
authors.lastname: Mori
authors.forename: Shinji
authors.initials: S
authors.lastname: Nakao
mesh_terms: D000208:Acute Disease; D000293:Adolescent; D000328:Adult; D000368:Aged; D016026:Bone Marrow Transplantation / Q000009:adverse effects / Q000276:immunology / Q000379:methods*; D002648:Child; D002675:Child, Preschool; D015331:Cohort Studies; D020022:Genetic Predisposition to Disease; D005838:Genotype; D006086:Graft vs Host Disease / Q000209:etiology* / Q000235:genetics / Q000276:immunology; D019337:Hematologic Neoplasms / Q000235:genetics* / Q000276:immunology / Q000601:surgery*; D006801:Humans; D007223:Infant; D008875:Middle Aged; D054596:Protein Tyrosine Phosphatase, Non-Receptor Type 22 / Q000235:genetics* / Q000276:immunology; D055815:Young Adult
chemical_list: C516765:PTPN22 protein, human; D054596:Protein Tyrosine Phosphatase, Non-Receptor Type 22