Elsevier

Journal of Clinical Virology

Volume 84, November 2016, Pages 64-69
Journal of Clinical Virology

Clinical significance of the single nucleotide polymorphism TLR2 R753Q in heart transplant recipients at risk for cytomegalovirus disease

https://doi.org/10.1016/j.jcv.2016.10.003Get rights and content

Highlights

  • Evaluation of TLR2 R753Q polymorphism in relation to CMV infection.

  • HTX were screened in relation to clinical parameters.

  • Targeted antiviral prophylaxis is more important than polymorphism.

Abstract

Background

The toll-like receptor 2 (TLR2) is a significant component of innate immunity against cytomegalovirus (CMV) infection but information on the clinical significance of the single nucleotide polymorphism (SNP) (R753Q) is conflicting.

Objectives

The inconsistent observations of the immunological and clinical significance of the TLR2 R753Q polymorphism for CMV infection indicates the influence of confounders.

Study design

The presence of the TLR2 polymorphism was determined by a genotyping assay of 175 HTX patients and 281 healthy blood donors and evaluated in relation to selected virological and clinical parameters.

Results

Relative frequency of TLR2 polymorphism was similar in HTX patients and blood donors (homozygous wild-type, 94.3% vs. 94.0%; heterozygous, 5.1% vs. 5.7%; homozygous mutated, <1%). CMV viremia was detectable in 108 (61.7%) of HTX patients. The TLR2 polymorphism was neither associated with occurrence or level of CMV infection nor with survival, graft failure or rejection, or CMV serostatus of patient before transplantation. Nevertheless, CMV viremia occurred in 83.1% of R+/D+, 77.1% of R+/D-, and 64.3% of R-/D+ patients. Time of first CMV viremia was in R-/D+ patients later than in CMV-seropositive patients (median, 182 days versus 23 days; P < 0.001) corresponding to the duration of antiviral prophylaxis in R-/D+ patients.

Conclusions

The TLR2 R753Q polymorphism is extremely rare in the general population and HTX patients. Screening for this risk factor of CMV disease may not be cost-effective in contrast to testing for CMV viremia.

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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