医学
类风湿性关节炎
甲氨蝶呤
P-糖蛋白
抗药性
地塞米松
流式细胞术
关节炎
免疫学
羟基氯喹
药品
来氟米特
淋巴细胞
流出
药理学
内科学
疾病
多重耐药
遗传学
2019年冠状病毒病(COVID-19)
传染病(医学专业)
微生物学
生物
作者
Shizuyo Tsujimura,Kazuyoshi Saito,Masao Nawata,Shingo Nakayamada,Yoshiya Tanaka
标识
DOI:10.1136/ard.2007.070821
摘要
Objective:
P-glycoprotein (P-gp), a member of the ATP-binding cassette transporter family, causes drug resistance by exclusion of intracellular drugs. Here, we elucidate the clinical relevance of P-gp expression on lymphocytes to drug resistance in patients with rheumatoid arthritis (RA). Methods:
P-gp expression on lymphocytes from 20 normal volunteers and 100 RA patients was analysed by flow cytometry. Drug exclusion analysis of lymphocytes was conducted by radioisotope-labelled dexamethasone. Results:
P-gp was overexpressed on RA lymphocytes compared with normal lymphocytes. P-gp expression levels were higher in partial responders with a Disease Activity Score (DAS) 28-3 of >5.1 despite taking at least two disease-modifying antirheumatic drugs (DMARDs) or one DMARD and corticosteroids for at least 2 years. P-gp expression levels correlated with DAS28-3. Intracellular dexamethasone levels (IDLs) in RA lymphocytes decreased according to P-gp expression. Tacrolimus, a P-gp inhibitor, restored IDLs in RA lymphocytes. P-gp overexpression in patients with highly active RA was suppressed by methotrexate but enhanced by corticosteroids. Furthermore, infliximab (3 mg/kg) resulted in improvement of RA disease activity, reduction of P-gp and recovery of IDLs. Conclusions:
P-gp overexpression on lymphocytes might cause efflux of corticosteroids and DMARDs, P-gp substrates, from lymphocytes, resulting in drug resistance in patients with highly active RA. P-gp inhibition/reduction could overcome such drug resistance. Measurement of P-gp expression on lymphocytes could be a potentially useful marker for assessing drug resistance in RA, and may be suitable for selecting infliximab or DMARDs including tacrolimus for RA treatment.
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