Levels of Forkhead Box P3 (FOXP3) Transcripts in Kidney Transplant Recipients is Associated With Post-Transplant Cytomegalovirus Viremia

BACKGROUND AND AIMS
The forkhead box P3 (FOXP3) transcription factor is essential for the differentiation of T regulatory cells, which are major regulators of immune tolerance and immunologic activity. Quantification of the FOXP3 mRNA in peripheral blood might be clinically useful. Considering possible post-transcriptional regulation of FOXP3 mRNA, we tested the hypothesis that a low level of FOXP3 is associated with a higher risk of cytomegalovirus (CMV) viremia, in kidney transplant recipients (KTRs).

METHOD
Blood samples were collected the first day after transplantation from incident adult kidney transplant recipients. Ribonucleic acid was extracted from peripheral blood mononuclear cells and used in quantitative reverse transcription polymerase chain reaction. Levels of FOXP3 were measured using two primers differentiating mRNA FOXP3 and pre-mRNA FOXP3 (pre-FOXP3), both primers were normalized to the reference gene β-actin. We defined viremia with CMV as the finding of more than 1000 copies per mL of CMV DNA in plasma, at least once, within 3 months after transplantation. A ratio of FOXP3 to pre-FOXP3 was calculated and compared, using Mann–Whitney U-test according to CMV viremia status. Finally using receiver operating characteristics, we calculated are under the curve.

RESULTS
Of 340 patients enrolled, 24 experienced post-transplant CMV viremia. The median ratio of FOXP3 to pre-FOXP3 was lower in those diagnosed with post-transplant CMV viremia, compared to those who were not 6.8 [1.2–11.3] versus 12.2 [3.5–28.9] P < 0.01, respectively. Receiver operating characteristics yielded an area under the curve of 66.7% P < 0.01.

CONCLUSION
Our data shows an association between low levels of FOXP3 and risk for post-transplant CMV infection in kidney transplant recipients.