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
- Transplantation: Clinical - Biomarkers
November 04, 2022 | Location: Exhibit Hall, Orange County Convention Center‚ West Building
Abstract Time: 10:00 AM - 12:00 PM
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 infection | Healthy Control | P-Value Group 1 vs Group 2 | P-value Group 1 vs Group 3 | P-value Group 2 vs Group 3 |
| TLR-2 | 11.5±3.1 | 22.7±8.1 | 28.1±9.6 | <0.001 | <0.001 | >.05 |
| TLR-4 | 6.1± 1.3 | 8.2± 2.2 | 12.4±4.1 | <0.001 | <0.001 | <0.02 |
Funding
- Government Support – Non-U.S.