ASN's Mission

To create a world without kidney diseases, the ASN Alliance for Kidney Health elevates care by educating and informing, driving breakthroughs and innovation, and advocating for policies that create transformative changes in kidney medicine throughout the world.

learn more

Contact ASN

1401 H St, NW, Ste 900, Washington, DC 20005

email@asn-online.org

202-640-4660

The Latest on Twitter

Kidney Week

Abstract: FR-PO768

Genetic Polymorphism and Serum Levels of Toll-Like Receptors (TLR-2 and TLR-4) in Renal Transplant Recipients With and Without Cytomegalovirus (CMV) Infection

Session Information

Category: Transplantation

  • 2002 Transplantation: Clinical

Authors

  • Mahajan, Sandeep, All India Institute of Medical Sciences, New Delhi, Delhi, India
  • Rizwan, Arshi, All India Institute of Medical Sciences, New Delhi, Delhi, India
Background

Viral infections like CMV are important cause of morbidity, mortality & limited graft survival in RTRs. TLR-2 & TLR-4 play important role in innate immune response & regulating production of antiviral peptides & inflammatory cytokines. Reduced TLR expression & polymorphisms (TLR2: Arg677Trp & Arg753Gln, TLR4: Asp299Gly & Thr399Ile) are associated with blunted immunological response & higher infectious complications. No study has looked at TLR expression & polymorphisms in RTRs & their association with infectious complications like CMV. Identifying this population at higher risk of infections can help in individualizing immunosuppressive therapy

Methods

85 consenting RTRs (35 with CMV & 50 without CMV infection) & 50 healthy controls were studied. All RTRs were on standard triple drug immunosuppression of Tacrolimus, MMF & steroids. Patients given gancylovir prophylaxis, rATG induction and with recent infection & anti-rejection therapy were excluded. Diagnosis of CMV infection was based on blood quantitative CMV DNA PCR testing (>500 copies/ml), done as per protocol at 45 days, 3, 6, 9 & 12 months post-RT and/or as per clinical need. Allele-specific polymorphisms were studied on extracted DNA samples by using PCR-based genotyping assay and serum levels of TLR-2 & TLR-4 were determined by using commercially available ELISA kits

Results

Mean age and gender distribution were similar in three groups. CMV infection was symptomatic in 23 (60 %) patients & all presented with history of fever & diarrhea.
As shown in table: RTRs having CMV infection had lower serum TLR2 and TLR4 values as compared to other groups. While, RTRs without CMV infection only had lower TLR4 levels as compared to controls. None of studied subject showed polymorphism in either TLR-2 or TLR-4 genes

Conclusion

We found that RTRs with CMV disease had lower serum TLR-2 & TLR-4 levels as compared to RTRs without CMV infection & healthy controls. However, we did not document any polymorphism in studied genes. These results require further validation in larger studies

Serum
Concentration
(pg/mL) (mean ± SD)
RTRs with CMV infection

RTRs without CMV infectionHealthy Control P-Value Group 1 vs Group 2P-value Group 1 vs Group 3P-value Group 2 vs Group 3
TLR-211.5±3.122.7±8.128.1±9.6<0.001<0.001>.05
TLR-4 6.1± 1.38.2± 2.212.4±4.1<0.001<0.001<0.02

Funding

  • Government Support – Non-U.S.