SAT-455 TACROLIMUS MAY REGULATE PATHOGENIC TH17 CELLS IN LUPUS NEPHRITIS REFRACTORY PATIENTS

Abstract

About 15-30% of Lupus Nephritis (LN) patients do not respond to first-line immunosuppressive therapy. Increased pathogenic (CD4+IL-17+IFN-γ) Th-17 cell population has been reported in such patients. Pathogenic Th-17 cells are know n to express P-glycoprotein (P-gp) that may efflux out glucocorticoids and thus contribute to resistance to treatment. In this in vitro study we evaluated the effect of Tacrolimus on pathogenic Th-17 population in refractory Lupus Nephritis patient’s. 10 Lupus Nephritis patients (mean age 34.06±10.84, all females) who were refractory to the cyclophosphamide treatment were recruited. Their Peripheral blood were collected in heparinized vial and stimulated with PMA & Ionomycin and co-cultured with or without Tacrolimus for 24 hour. Pathogenic Th-17 population was analyzed using flow-cytometer. Tacrolimus significantly (p=0.006) reduced, 5.5±1.1% to 4.24±1.3%, the frequency of Th-17 cells in PMA/ionomycin stimulated PBMCs of these patients. Similarly, frequency of pathogenic Th17 cells was also significantly (p=0.004) reduced, 1.75±.14% to 0.53±0.16%, by Tacrolimus. Additionally, Tacrolimus significantly (p=0.001) reduced, 90.5±5.67% to 67.53±8.89%, the expression of P- gp on pathogenic Th-17 cells. Tacrolimus not only significantly reduced the frequency of Pathogenic Th17 cell population but also expression of P-gp on Pathogenic Th-17. It may have potential to reverse treatment non-responsiveness in lupus nephritis.