MDR1 GENE-EXPRESSION IN LYMPHOCYTES OF PATIENTS WITH RENAL-TRANSPLANTS

The MDR1 gene, a multidrug resistance gene, codes for P-glycoprotein w hich pumps hydrophobic drugs out of the cells. Since cyclosporins also bind to P-glycoprotein and might be pumped by this transmembrane prot ein, we determined the expression of the MDR1 gene in the lymphocytes of 32 patients with renal transplants. MDR1 RNA expression of lymphocy tes was measured by slot blot analysis and compared to the expression of drug-sensitive KB-3-1 cells and multidrug-resistant KB-8-5 cells. M DR1 RNA expression was detected in the lymphocytes of 9 (28%) patients , whereas no expression was seen in the remaining 23 patients. No asso ciation between MDR1 RNA expression and transplant function or hematol ogical parameters was observed. However, none of the 6 patients who ha d transplants for more than 40 months expressed the MDR1 gene in their lymphocytes. In conclusion, expression of the MDR1 gene does occur in lymphocytes of patients with renal transplants and might reduce the i mmunosuppressive efficacy of cyclosporins through enhanced efflux of c yclosporins.