Recipient PTPN22 -1123 C/C Genotype Predicts Acute Graft-versus-Host Disease after HLA Fully Matched Unrelated Bone Marrow Transplantation for Hematologic Malignancies

J. Luis Espinoza, Akiyoshi Takami, Makoto Onizuka, Yasuo Morishima, Takahiro Fukuda, Yoshihisa Kodera, Hideki Akiyama, Koichi Miyamura, Takehiko Mori, Shinji Nakao

Research output: Contribution to journalArticle

5 Citations (Scopus)

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.

Original languageEnglish
Pages (from-to)240-246
Number of pages7
JournalBiology of Blood and Marrow Transplantation
Volume19
Issue number2
DOIs
Publication statusPublished - 2013 Feb 1

Keywords

  • Lymphoid specific phosphatase
  • Promoter gene variant
  • Rs2488457
  • Single nucleotide variation
  • Unrelated donor

ASJC Scopus subject areas

  • Hematology
  • Transplantation

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