INTRODUCTION: Among elderly allograft recipients non-melanoma skin cancer (NMSC) is the most common malignancy. We have previously shown that malignancies are associated with a higher intensity of ciclosporin A (CsA)-induced immunosuppression. METHOD: Fifty-five long-term elderly renal transplant patients with a stable transplant function had regular skin examinations. The expression of the nuclear factor of activated T cells (NFAT)-regulated genes (interleukin-2, granulocyte-macrophage colony stimulating-factor, interferon-gamma) was determined by real-time PCR at CsA trough levels and two h after oral intake. RESULTS: The CsA dose was 2.0 mg/kg (0.95-3.50), with CsA trough level (C0) level 97 microg/L (33-157) and CsA two-h level (C2) 538 microg/L (350-1228). NMSC was diagnosed in 14/55 patients (25.4%). A total of 85.7% of allograft recipients with NMSC were male (p < 0.005). Age, time after transplantation, CsA dose, CsA C0 and C2 level were comparable in both groups. NFAT-regulated gene expression was signficantly lower in patients with skin cancer compared with patients without skin cancer [4.94% (0.91-13.4) vs. 11.6% (3.3-40.8), p < 0.001). CONCLUSION: The unproportional high incidence of NMSC in elderly long-term kidney-transplanted patients correlates with a lower NFAT-regulated gene expression which is a surrogate biomarker for a higher degree of functional immunosuppression. Further studies are required to determine whether the reduction of CsA with an increased NFAT-regulated gene expression is associated with a lower NMSC incidence.
INTRODUCTION: Among elderly allograft recipients non-melanoma skin cancer (NMSC) is the most common malignancy. We have previously shown that malignancies are associated with a higher intensity of ciclosporin A (CsA)-induced immunosuppression. METHOD: Fifty-five long-term elderly renal transplant patients with a stable transplant function had regular skin examinations. The expression of the nuclear factor of activated T cells (NFAT)-regulated genes (interleukin-2, granulocyte-macrophage colony stimulating-factor, interferon-gamma) was determined by real-time PCR at CsA trough levels and two h after oral intake. RESULTS: The CsA dose was 2.0 mg/kg (0.95-3.50), with CsA trough level (C0) level 97 microg/L (33-157) and CsA two-h level (C2) 538 microg/L (350-1228). NMSC was diagnosed in 14/55 patients (25.4%). A total of 85.7% of allograft recipients with NMSC were male (p < 0.005). Age, time after transplantation, CsA dose, CsA C0 and C2 level were comparable in both groups. NFAT-regulated gene expression was signficantly lower in patients with skin cancer compared with patients without skin cancer [4.94% (0.91-13.4) vs. 11.6% (3.3-40.8), p < 0.001). CONCLUSION: The unproportional high incidence of NMSC in elderly long-term kidney-transplanted patients correlates with a lower NFAT-regulated gene expression which is a surrogate biomarker for a higher degree of functional immunosuppression. Further studies are required to determine whether the reduction of CsA with an increased NFAT-regulated gene expression is associated with a lower NMSC incidence.
Authors: John R Greenland; Tiffany Chong; Angelia S Wang; Emily Martinez; Pavan Shrestha; Jasleen Kukreja; Steven R Hays; Jeffrey A Golden; Jonathan P Singer; Qizhi Tang Journal: Am J Transplant Date: 2018-05-22 Impact factor: 8.086
Authors: Sara Bremer; Nils T Vethe; Morten Skauby; Margrete Kasbo; Elisabet D Johansson; Karsten Midtvedt; Stein Bergan Journal: Br J Clin Pharmacol Date: 2017-08-16 Impact factor: 4.335
Authors: Elliot D Blue; S Caleb Freeman; Marissa B Lobl; Dillon D Clarey; Rose L Fredrick; Ashley Wysong; Melodi Javid Whitley Journal: JID Innov Date: 2022-03-30