Clinical significance of the single nucleotide polymorphism TLR2 R753Q in heart transplant recipients at risk for cytomegalovirus disease
Section snippets
Background
Innate immunity plays an important role in the prevention and control of opportunistic pathogens in solid-organ transplantation. Cytomegalovirus (CMV) is one of the most significant viral opportunistic pathogens in solid-organ and bone-marrow transplantation [1]. The innate immune response to CMV is initiated by recognition of the viral envelope glycoproteins B (gB) and H (gH) by TLR2. This TLR2-CMV interaction initiates a cascade of intracellular signaling events that lead to the production of
Objectives
The conflicting observations of the immunological and clinical significance of the TLR2 R753Q polymorphism for CMV infection indicates the influence of confounders. To evaluate the significance of the TLR2 R753Q polymorphism together with other clinical and laboratory characteristics of solid-organ transplant patients, we evaluated a well-characterized cohort of heart transplant recipients (HTX) in relation to occurrence of CMV infection.
Study population
The present study was based on an ongoing observational, cross-sectional study of HTX patients with stratification for CMV status of organ donor and recipient (Medical University of Vienna Biobank Study). So far, 320 patients have been included in this study from 2009 to 2014. For the present study, only consecutive patients with archived leukocyte preparations available for DNA isolation were included (n = 175). Patients included in the present study received a heart transplant between 1991 and
Results
The study population included a total of 175 patients who underwent allogeneic heart transplantation. Key demographic and clinical characteristics of the 175 HTX patients are summarized in Table 1. The mean age of the patients at the time of HTX surgery was 49 years (SD, 14 years) and the majority of patients (74.9%) were male. The most common reason for heart transplantation was dilated cardiomyopathy (57.1%) and the majority of patients were still alive (93.7%) after a mean observation period
Discussion
Current evidence on the significance of the TLR2 R753Q polymorphism in CMV infection is conflicting. Two studies on the relevance of the TLR2 R753Q polymorphism in a total of >800 liver transplant recipients found a significantly increased risk for severe CMV disease in patients with a mutated genotype [9], [10]. Another study evaluated the polymorphism in 265 kidney-transplant patients and found no significant effect in relation to graft survival, renal function, or incidence of opportunistic
Conclusions
We evaluated the risk for CMV infection and tissue-invasive disease in relation to this polymorphism in a further cohort of patients – HTX recipients – to test for potential confounders that may explain the discrepant observations in previous studies. The most significant prognostic parameter for CMV infection was the CMV-specific serological match between recipient and donor in HTX patients receiving optimized antiviral prophylaxis. The TLR2 R753Q polymorphism may influence the natural course
Competing interests
All authors declare no conflict of interest.
Contributors
Participated in research design: Steininger C.Participated in the writing of the paper: Schneider M., Steininger C.Participated in the performance of the research: Schneider M., Matiqi T., Rieder F., Strassl R.Contributed patient material: Andreas M., Zuckermann A., Jungbauer C.Participated in data analysis: Schneider M., Kundi M., Steininger C.
Funding
This work was supported by a research grant of the Austrian Science Funds #P25353-B21. Schneider M. is a recipient of a DOC Fellowship of the Austrian Academy of Sciences.
Ethical approval
The study was performed in accordance with the Declaration of Helsinki and good clinical practice guidelines and was approved by the local ethics committee (EK2179/2013).
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Cytomegalovirus and other herpesviruses after hematopoietic cell and solid organ transplantation: From antiviral drugs to virus-specific T cells
2022, Transplant ImmunologyCitation Excerpt :Without prophylaxis, approximately 80% of CMV seropositive allo-HCT patients will experience CMV infection (viremia), and approximately 30% of patients with CMV viremia will develop CMV disease [30]. The risk factors responsible for the increased incidence of CMV infection in SOT recipients are CMV serostatus of the donor (D+) and recipient (R−) (from high to low risk: D+/R− > D+/R+ > D−/R+ > D−/R−), a type of organ transplant (from high to low risk: intestine > lung > pancreas > heart > liver/kidney), immunological sensitization of recipients with a high degree of HLA mismatch, types of immunosuppressive regimen (by using T lymphocyte-depleting antibodies such as anti-thymocyte globulin), coinfection with HHV-6 or HHV-7, and the existence of specific genetic polymorphisms of genes involved in innate immunity (such as Toll-like receptors 2 and 4) [31–39]. Serostatus of the donor and recipient is a key predictor of the risk of viral infection after transplantation.
Toll-like Receptor 4 Single-Nucleotide Polymorphisms and Heart Transplant Rejection
2018, Transplantation ProceedingsCitation Excerpt :No TLR4 SNPs were investigated as possible candidates for increased level of heart transplant rejection, thus comparing results of this study to any other was not possible. In fact, the only TLR investigated in this group of patients was Toll-like receptor 2 (TLR2) and increased susceptibility to cytomegalovirus infection, but not to rejection of the transplanted organ [8]. For this reason, stating that TLRs in general may play an important role in influencing heart transplant rejection or not would be farfetched according to none of the data presented in Medline, PubMed, and Scholar databases.