INTRODUCTION: In rheumatoid arthritis (RA), P-glycoprotein (P-gp) expression on activated B cells is associated with active efflux of intracellular drugs, resulting in drug resistance. CXCR4 is associated with migration of B cells. This study was designed to elucidate the relevance of P-gp expression on CXCR4+ B cells to clinical manifestations in refractory RA. METHODS: CD19+ B cells were analyzed using flow cytometry and immunohistochemistry. RESULTS: P-gp was highly expressed especially on CXCR4+CD19+ B cells in RA. The proportion of P-gp-expressing CXCR4+ B cells correlated with disease activity, estimated by Simplified Disease Activity Index (SDAI), and showed marked expansion in RA patients with high SDAI and extra-articular involvement. In highly active RA, massive infiltration of P-gp+CXCR4+CD19+ B cells was noted in CXCL12-expressing inflammatory lesions of RA synovitis and RA-associated interstitial pneumonitis. In RA patient with active extra-articular involvement, intracellular dexamethasone level (IDL) in lymphocytes diminished with expansion of P-gp+CXCR4+ CD19+ B cells. Adalimumab reduced P-gp+CXCR4+ CD19+ B cells, increased IDL in lymphocytes, and improved the clinical manifestation and allowed tapering of concomitant medications. CONCLUSIONS: Expansion of P-gp+CXCR4+ B cells seems to be associated with drug resistance, disease activity and progressive destructive arthritis with extra-articular involvement in RA.
INTRODUCTION: In rheumatoid arthritis (RA), P-glycoprotein (P-gp) expression on activated B cells is associated with active efflux of intracellular drugs, resulting in drug resistance. CXCR4 is associated with migration of B cells. This study was designed to elucidate the relevance of P-gp expression on CXCR4+ B cells to clinical manifestations in refractory RA. METHODS:CD19+ B cells were analyzed using flow cytometry and immunohistochemistry. RESULTS:P-gp was highly expressed especially on CXCR4+CD19+ B cells in RA. The proportion of P-gp-expressing CXCR4+ B cells correlated with disease activity, estimated by Simplified Disease Activity Index (SDAI), and showed marked expansion in RA patients with high SDAI and extra-articular involvement. In highly active RA, massive infiltration of P-gp+CXCR4+CD19+ B cells was noted in CXCL12-expressing inflammatory lesions of RA synovitis and RA-associated interstitial pneumonitis. In RA patient with active extra-articular involvement, intracellular dexamethasone level (IDL) in lymphocytes diminished with expansion of P-gp+CXCR4+ CD19+ B cells. Adalimumab reduced P-gp+CXCR4+ CD19+ B cells, increased IDL in lymphocytes, and improved the clinical manifestation and allowed tapering of concomitant medications. CONCLUSIONS: Expansion of P-gp+CXCR4+ B cells seems to be associated with drug resistance, disease activity and progressive destructive arthritis with extra-articular involvement in RA.
Entities:
Keywords:
B cell; CXCR4; P-glycoprotein; rheumatoid arthritis
Authors: E E Perez-Guerrero; L Gonzalez-Lopez; J F Muñoz-Valle; J C Vasquez-Jimenez; M Ramirez-Villafaña; E N Sanchez-Rodriguez; S R Gutierrez-Ureña; S Cerpa-Cruz; E A Aguilar-Chavez; E G Cardona-Muñoz; M L Vazquez-Villegas; A M Saldaña-Cruz; N A Rodriguez-Jimenez; N S Fajardo-Robledo; J I Gamez-Nava Journal: Inflammopharmacology Date: 2018-09-12 Impact factor: 4.473