Peripheral Treg count and it's determinants in unsensitized and sensitized chronic kidney disease patients


Topal C., KÖKSOY S., Süleymanlar G., Yakuboğlu G., Ersoy F. F.

INTERNATIONAL UROLOGY AND NEPHROLOGY, vol.45, no.6, pp.1647-1652, 2013 (SCI-Expanded) identifier identifier identifier

  • Publication Type: Article / Article
  • Volume: 45 Issue: 6
  • Publication Date: 2013
  • Doi Number: 10.1007/s11255-013-0460-9
  • Journal Name: INTERNATIONAL UROLOGY AND NEPHROLOGY
  • Journal Indexes: Science Citation Index Expanded (SCI-EXPANDED), Scopus
  • Page Numbers: pp.1647-1652
  • Keywords: Chronic kidney disease (CKD), Panel reactive antibody (PRA), Treg, HLADR, Immunoregulation, Kidney transplantation, REGULATORY T-CELLS, RENAL-FAILURE, DIALYSIS, CANCER
  • Akdeniz University Affiliated: Yes

Abstract

An increase in the number of circulating endothelial cells (CEC) indicates endothelial damage and the risk of cardiovascular disease. The aim of our study was to investigate the association of CEC with various clinical parameters in pediatric renal transplant recipients.

CEC, defined as CD45(-)CD146(+), were enumerated by flow cytometry from the peripheral blood of 50 pediatric renal transplant recipients and 20 healthy controls. Clinical parameters, including renal function tests, fasting blood glucose, serum cholesterol and triglyceride, cyclosporine A (CsA) (trough and 2nd-hour) and tacrolimus (tac) trough blood levels and their association with CEC numbers were analyzed.

CEC numbers of patients were higher than those of controls (respectively, 128 +/- 89 cells/ml (42-468 cells/ml), 82 +/- 33 cells/ml (32-137 cells/ml), p = 0.024). There was a statistically significant negative correlation between CEC numbers and glomerular filtration rate (GFR) (r = -0.300, p = 0.012). There was also a statistically positive association between CEC numbers and transplant duration as well as cyclosporine trough level (respectively, r = 0.397, p = 0.004, r = 0.714, p = 0.004). CEC numbers in patients on tac and CsA were similar (p = 0.716).

Our results demonstrate that renal transplant recipients with high CsA trough blood level, longer transplant duration, and lower GFR, are at greater risk of developing endothelial damage.

Sensitization to HLA antigens resulting in anti-HLA antibodies (panel reactive antibodies; PRA) is a major problem in chronic kidney disease (CKD) patients awaiting transplantation. Induction of anti-HLA antibodies normally occurs through blood transfusion, pregnancy and prior transplantation. However, some patients develop these antibodies for unknown immunological reasons. It is hypothesized that deviations in immune regulation may account for PRA positivity in these patients. We, therefore, investigated whether a quantitative deficiency in peripheral natural regulatory T cells (CD4(+)CD25(high)Foxp3(+); nTreg) plays a role in this phenomenon.