FRI0264 Role of p-gp in pathogenic conversion of th17 cells in lupus nephritis leading to glucocorticoid resistance. (12th June 2018)

• Record Type: Journal Article
• Authors: Jaiswal, A.; Rai, M.K.; Agarwal, V.; Prasad, N.
• Is Part Of: Annals of the rheumatic diseases. Volume 77(2018)Supplement 2
• Page Start: 671
• Page End: 672
• Publication Date: 2018-06-12
• Subjects: Rheumatism -- Periodicals; 616.723005
• DOI: 10.1136/annrheumdis-2018-eular.6457
• Languages: English
• ISSNs: 0003-4967

Abstract

Abstract : Background: Th17 cells and cytokine IL-17 are mainly involved in autoimmunity. Recently IL-17/IFN-g double-positive Th17 cell were found to be allied with inflammatory diseases. P-glycoprotein (P-gp) +ve 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 +ve Th17 are one of key pharmacokinetic and pharmacodynamic modulator liable for steroid resistance in lupus nephritis (LN). Objectives: We planned to study the frequency of P-gp expressing pathogenic Th17 cells in steroid responsive and non-responsive steroid 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 responsive (n=52; mean age 34.06±10.84) and non-responsive (n=25; mean age 37.29±13.73) patients. We also included 10 age and sex matched healthy controls. All patients were biopsy proven LN. 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=0.006) and IL-17/IFN-g doublepositive Th17 (<0.001) cells in non-responsive as compared to responsive 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 nonresponsive;45.0%; 30.27% and 30.1% cells expressed P-gp in responsive group; and 30.91%; 15.51% and 15.62% in healthy control respectively. Conclusions: Higher frequency of IL-17/IFN-g doublepositive Th17 cell with P-gp expression may be associated immunological and pharmacological factor for steroid resistance in LN. Disclosure of Interest: None declared