Potential of B-cell-targeting therapy in overcoming multidrug resistance and tissue invasiveness associated with P-glycoprotein expressing-B cell compartments

Abstract

Rheumatoid arthritis (RA) is a systemic autoimmune mediated inflammatory disease characterized by progressive joint damage and extra-articular organ manifestations. Among the effector pathways and cells involved in the development of RA, activated B cells play a pivotal role in the pathological process of RA. P-glycoprotein (P-gp), a member of ATP-binding cassette transporters, is induced on the cell membrane by certain stimuli. P-gp transports various drugs from the cytoplasm to the cell exterior, resulting in the development of drug resistance. P-gp expression on B cells appears in patients with RA as the disease activity increases, and treatment of these patients’ results in modification of over-expression of P-gp on activated B cells. Evidence suggests that P-gp expressing-activated B cells play important roles in the pathogenesis and treatment resistance in RA through the efflux of intracellular drugs and progression of infiltration in inflammatory lesions. Therapies designed to target activated B cells might overcome refractory RA. Identification of the subsets of peripheral activated B cells that express P-gp in RA patients might help the selection of suitable treatment strategy.