IL-17/IFN-G Double-positive TH17 cells selectively express P-Glycoprotein and are refractory to glucocorticoid in minimal change disease

BACKGROUND: Th17 cells and cytokine IL-17 are involved in many autoimmune diseases. Recently; IL-17/IFN-g double-positive Th17 cell were found to be allied with inflammatory diseases. P-glycoprotein (P-gp) positive Th17 cells are refractory to steroid. P-gp on lymphocyte effluxes out steroid and prevents its action. We conducted this study with hypothesis that P-gp positive IL-17/IFN-g double positive Th17 are one of key pharmacokinetic and pharmacodynamic modulator liable for steroid resistance in nephrotic syndrome. AIM OF THE STUDY: We planned to study the frequency of P-gp expressing pathogenic Th17 cells in steroid sensitive (SSNS) and steroid resistant (SRNS) patients. METHODS: We analysed the frequency of pathogenic IL-17/ IFN-g double-positive Th17 lymphocytes and P-gp expression on their surface by flowcytometry in SSNS (n=32; mean age 9.06±5.84) and SRNS (n=28; mean age 11.29±3.73) patients. We also included 15 age and sex matched healthy controls. All patients were biopsy proven MCD and all patients were treated with steroid. All patients were recruited as per criteria of ISKDC. RESULTS: We found a significant increase in the frequency of Th1 (p=0.001); Th17 (p=0.006) and IL-17/IFN-g double-positive Th17 (p<0.001) cells in SRNS as compared to SSNS patients and healthy controls (p<0.001). Of the total Th1; Th17 and pathogenic Th17; 78.45%; 72.37% and 95.8% cells expressed P-gp on their surface in SRNS;45.0%; 30.27% and 30.1% cells expressed P-gp in SSNS group; and 30.91%; 15.51% and 15.62% in healthy control respectively. CONCLUSIONS: Higher frequency of IL-17/IFN-g double-positive Th17 cell with P-gp expression may be associated immunological and pharmacological factor for steroid resistance in minimal change disease.