Relation between costimulatory molecule polymorphism and hepatitis B infections in hematopoietic stem cell transplant recipients

Exp Clin Transplant. 2014 Aug;12(4):357-66. doi: 10.6002/ect.2013.0035. Epub 2013 Oct 31.

Abstract

Objectives: Costimulatory gene polymorphisms have been proposed to affect the hepatitis B virus pathogenesis by affecting regulation of immune responses. The association between costimulatory molecule gene polymorphisms including CTLA4, PD.1, ICOS, and CD28 with hepatitis B virus infection has been evaluated in hematopoietic stem cell transplant patients.

Materials and methods: In a cross-sectional study, single-nucleotide polymorphisms in the loci of the costimulatory molecules were analyzed in 3 study groups. Hepatitis B virus infection was evaluated in plasma samples of each allogeneic and autologous hematopoietic stem cell transplant patients by a third generation HBsAg enzyme-linked immunosorbent assay kit according to the manufacturer 's instructions.

Results: Hepatitis B virus infection was found in 19 of 72 allogeneic (26.3%) and 26 of 59 autologous patients (44.1%). The T allele of CTLA4-318 and CC genotype of CD28+17 polymorphisms are significantly more frequent in hepatitis B virus-infected allogeneic hematopoietic stem cell transplant patients. The CC genotype of CD28 +17 was seen more frequently in hepatitis B virus-infected allogeneic hematopoietic transplant patients. The C allele of the PD.1.9 was seen more frequently in hepatitis B virus-infected allogeneic hematopoietic patients experiencing graft-versus-host disease. Also, the frequency of CT genotype and T allele of the PD.1.9 was significantly increased in hepatitis B virus-infected allogeneic hematopoietic stem cell transplant patients experiencing low-grade graft-versus-host disease.

Conclusions: Associations of CTLA4 -318 and CD28 +17 with hepatitis B virus infection in allogeneic hematopoietic stem cell transplant patients was reported, also it was determined that PD.1.9 genotypes and hepatitis B virus infection in allogeneic hematopoietic stem cell transplant patients experiencing low-grade graft-versus-host disease was associated. However, better evaluations of the relations between costimulatory gene polymorphisms with hepatitis B virus infection in hematopoietic stem cell transplant patients requires further investigations.

MeSH terms

  • Adolescent
  • Adult
  • CD28 Antigens / genetics*
  • CTLA-4 Antigen / genetics*
  • Child
  • Cross-Sectional Studies
  • Female
  • Gene Frequency
  • Genetic Predisposition to Disease
  • Graft vs Host Disease / genetics
  • Graft vs Host Disease / immunology
  • Hematopoietic Stem Cell Transplantation / adverse effects*
  • Hepatitis B / diagnosis
  • Hepatitis B / genetics*
  • Hepatitis B / immunology
  • Humans
  • Inducible T-Cell Co-Stimulator Protein / genetics
  • Male
  • Middle Aged
  • Phenotype
  • Polymorphism, Genetic*
  • Programmed Cell Death 1 Receptor / genetics*
  • Risk Factors
  • Time Factors
  • Treatment Outcome
  • Young Adult

Substances

  • CD28 Antigens
  • CTLA-4 Antigen
  • CTLA4 protein, human
  • ICOS protein, human
  • Inducible T-Cell Co-Stimulator Protein
  • PDCD1 protein, human
  • Programmed Cell Death 1 Receptor