Objectives: An association between costimulatory molecule gene polymorphisms and viral infection after hematopoietic stem cell transplantation may be related to clinical outcomes, especially acute graftversus-host disease. Cytotoxic T-lymphocyte antigen 4 has been suggested as a crucial negative regulator of the immune system. In this study, our objective was to investigate the association between cytotoxic T-lymphocyte antigen-4 gene polymorphisms (including -1722 T/C, -1661 A/G, -318 C/T, and +49 A/G) and torque teno virus infection after hematopoietic stem cell transplantation in patients with and without acute graft-versus-host disease. Materials and Methods: Our study included 71 recipients. We evaluated cytotoxic T-lymphocyte antigen 4 gene polymorphisms using the polymerase chain reactionrestriction fragment length polymorphism method. Results: Our results showed that the GG genotype of the cytotoxic T-lymphocyte antigen 4 +49 A/G was significantly more frequent in transplanted patients infected with torque teno virus, whereas the AG genotype was more common in transplanted patients who did not have this infection. In addition, the -1661 AA and GA genotypes and -318 TC genotypes were significantly more frequent in transplanted patients infected with the virus and who had low-grade (grades I and II) acute graft-versus-host disease. Among those with grade I graft-versus-host disease, the GG genotype of the cytotoxic T-lymphocyte antigen 4+49 A/G was more frequent in transplanted patients with torque teno virus infection, whereas the AG genotype was higher in transplanted patients who did not have this infection.Conclusions: This is the first report indicating that cytotoxic T-lymphocyte antigen 4 gene polymorphism may be implicated in prevalence of torque teno virus infection after stem cell transplant. Further larger studies and evaluation of other costimulatory molecules are suggested.
Key words: Graft-versus-host disease, Single nucleotide polymorphisms, Stem cell transplantation, Viral infections
Introduction
Transfusion-transmitted viruses or TT viruses, classified into the family Circoviridae, genusAnellovirus, were originally isolated in 1997 from the serum of a Japanese patient with posttransfusion hepatitis of unknown cause. Torque teno virus (TTV) is a nonenveloped, circular, and single-stranded DNA virus with genome of negative polarity. 1,2 Torque teno virus infection is common among hepatitis patients and is presented worldwide in blood donors. Because TTV sequences can be detected in sera and liver tissues from patients with liver disease, it has been suggested that TTV would be responsible for some acute and chronic liver disorders and thereby many autoimmune diseases such as idiopathic hepatitis, idiopathic pulmonary fibrosis, aplastic anemia, systemic lupus erythematosus, and multiple sclerosis. However, the biologic nature of TTV has not yet been clearly defined. [3][4][5] The costimulatory molecules, including programmed cell death-1 (PD-1), cluster differentiation 28 (CD28), indu...