The Study on P-Glycoprotein Expression on Peripheral Lymphocytes of Refractory Rheumatoid Arthritis Patients

2018 ◽  
Vol 8 (6) ◽  
pp. 911-914
Author(s):  
Xueming Yao ◽  
Wukai Ma ◽  
Ying Huang ◽  
Qiaoyi Ning ◽  
Lei Hou ◽  
...  
2010 ◽  
Vol 37 (3) ◽  
pp. 512-520 ◽  
Author(s):  
KATSUNORI SUZUKI ◽  
KAZUYOSHI SAITO ◽  
SHIZUYO TSUJIMURA ◽  
SHINGO NAKAYAMADA ◽  
KUNIHIRO YAMAOKA ◽  
...  

Objective.Tacrolimus, a calcineurin inhibitor, is used for treatment of rheumatoid arthritis (RA). It also inhibits functions of P-glycoprotein, which is involved in drug resistance. We examined the mechanisms of early response to 2-week tacrolimus treatment in patients with RA.Methods.One hundred thirteen patients with refractory RA despite at least 3 antirheumatic agents, including methotrexate, were treated with tacrolimus (1.5–3 mg/day) and the response was assessed at 2 weeks. Expression of the multidrug resistance (MDR-1) gene and P-glycoprotein was assessed in peripheral blood mononuclear cells (PBMC) collected from 113 patients and 40 healthy subjects. The drug exclusion function by the P-glycoprotein was measured by the residual amount of intracellular tritium-labeled dexamethasone cell/medium ratio (C/M ratio).Results.The disease activity of enrolled patients was 5.8 ± 1.2 (mean ± SD) by DAS28 erythrocyte sedimentation rate. A good response to tacrolimus was noted at 2 weeks in 22 of 113 patients. At baseline, PBMC of patients with RA showed upregulated expression ofMDR-1gene and P-glycoprotein and low C/M ratio. The response to tacrolimus correlated with P-glycoprotein expression and C/M ratio. A significant improvement in C/M ratio was noted after 2 weeks of treatment. The C/M ratio correlated significantly with P-glycoprotein expression on CD4+ lymphocytes.Conclusion.Early efficacy of tacrolimus treatment depended on its inhibitory effect on the drug exclusion function of P-glycoprotein, leading to restoration of intracellular therapeutic levels of corticosteroids and clinical improvement. Evaluation of P-glycoprotein expression on lymphocytes is potentially useful for predicting the response to RA treatment.


2003 ◽  
Vol 2 (1) ◽  
pp. 25-26
Author(s):  
M Suleman ◽  
◽  
MB Chaudri ◽  
C Deighton ◽  
RB Hubbard ◽  
...  

Low dose methotrexate has been used successfully to treat patients with refractory rheumatoid arthritis.1 Methotrexate-induced pneumonitis occurs in about 1 to 5% of patients, although opportunistic infections have also been reported.1 We report a case of fatal pneumocystis carinii pneumonia (PCP) in an otherwise healthy female patient treated with methotrexate for rheumatoid arthritis and review the literature.


BMJ ◽  
1983 ◽  
Vol 287 (6394) ◽  
pp. 711-712 ◽  
Author(s):  
K Horslev-Petersen ◽  
J M Beyer ◽  
P Helin

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