Cytokine Levels in Transplant Recipients Associated with Cytomegalovirus

Cytomegalovirus seropositivity is an independent risk factor for atherosclerosis in patients with end stage renal disease (ESRD) and donor cytomegalovirus (CMV) seropositivity is associated with higher graft loss.

Without CMV prophylaxis, donor and recipient CMV seropositivity are detrimental factors for long-term renal allograft survival and post-transplant CMV infection whereas CMV prophylaxis prevented acute rejection (AR) and improved graft function.

Scientists at the University of Heidelberg (Germany) measured pre-operative plasma levels of the cytokines interleukin- 9 (IL-9), IL-21 and IL-23 in 117 patients with ESRD (aged 49.8 ± 16.3 years, 54 female) who underwent kidney transplantation. The aim was to evaluate associations of Th17-dependent cytokines with ESRD, CMV status and post-transplant outcome in kidney transplantation.

The plasma levels of IL-9, IL-21 and IL-23 were measured with a commercial test developed by Komabiotech (Seoul, South Korea) using enzyme-linked immunosorbent assay (ELISA) kits. Post-transplant CMV pp65 antigenemia was determined and the presence of more than three detectable CMV pp65 positive cells in 500,000 peripheral leukocytes was defined as reactivation or symptomatic infection. The CMV reactivation was confirmed by CMV-DNA detection in CMV pp65 antigen-positive patients. CMV DNA was extracted from blood samples and purified and amplification of CMV IE-1 gene DNA, a nested polymerase chain reaction (PCR) was performed in a GeneAmp PCR System 2400 thermocycler (Perkin Elmer, Norwalk, CT, USA).

The scientists found that IL-21 plasma levels were similar in patients and healthy controls, whereas IL-9 and IL-23 levels were significantly higher in ESRD patients. CMV-seronegative and –seropositive patients had significantly higher IL-23 plasma levels than controls. CMV-seropositive patients showed excessively higher IL-23 plasma levels than CMV-seronegative patients. Patients with post-transplant CMV reactivation had higher IL-23 plasma levels than patients without CMV reactivation. The pre-transplant IL-23 plasma levels of greater than 7 pg/mL are associated with a high risk of developing CMV disease during the first year post-transplant. High IL-23 plasma levels indicate a strong activation of Th17 lymphocytes, dendritic cells and macrophages.

The authors concluded that CMV-seropositive patient with high pre-transplant IL-23 should preferentially receive a CMV-seronegative graft in order to lower the risk of post-transplant CMV disease. IL-23 monitoring pre- and post-transplant might enable decisions concerning treatment options with the aim to decrease the risk of the post-transplant complications such as CMV disease and they speculate that CMV prophylaxis in renal transplant recipients might reduce the rate of cardiovascular death. The study was published on October 3, 2016, in the journal BMC Immunology.

Related Links:
University of Heidelberg
Komabiotech
Perkin Elmer