title: Expression of multidrug resistance-1 protein correlates with disease activity rather than the refractoriness to methotrexate therapy in rheumatoid arthritis.
abstract: Disease-modifying antirheumatic drugs (DMARDs) improve the disability and slow the progression of the joint damage in rheumatoid arthritis (RA). However, a large proportion of patients experience inefficacy by the end of 2 years. This loss of efficacy may be due to expression of multidrug resistance (MDR) proteins on lymphocytes. The objective is to study the expression of MDR protein on the peripheral blood lymphocytes in patients with RA and correlate it with the disease status and response to treatment. Twenty-eight patients were enrolled. Expression of MDR-1 by flow cytometry was carried out on lymphocytes at baseline and after 4 months of therapy. This expression was correlated with disease activity scores (DAS 28). There were 25 females with mean age of 48.13 years and median disease duration of 48 months. Eighteen patients were DMARD naive and ten were refractory to DMARD (methotrexate). The percentage of cells expressing MDR-1 in the DMARD-naive (p<0.O5) and DMARD-refractory (p<0.05) groups were significantly higher than the healthy controls at the baseline. The relative fluorescence intensity was significantly higher in the DMARD-refractory group (p<0.05) as compared to the DMARD-naive group. After 4 months of therapy, there was significant improvement in the D value (p<0.01) in the DMARD-naive group (treated with methotrexate only) and DMARD-refractory group (p<0.05). A significant correlation (r=0.563) between the DAS 28 scores and the D value (p=0.003) was observed. Expression of MDR-1 in RA correlated with disease activity status and improved with DMARD therapy. It is not related to the refractoriness to therapy with methotrexate.
authors.affiliation: Department of Immunology, Sanjay Gandhi Postgraduate Institute of Medical Sciences, Lucknow, India. vikasagr@sgpgi.ac.in
authors.forename: V
authors.initials: V
authors.lastname: Agarwal
authors.forename: S K
authors.initials: SK
authors.lastname: Mittal
authors.forename: R
authors.initials: R
authors.lastname: Misra
mesh_terms: D018435:ATP Binding Cassette Transporter, Subfamily B; D020168:ATP Binding Cassette Transporter, Subfamily B, Member 1 / Q000096:biosynthesis* / Q000378:metabolism; D000328:Adult; D001172:Arthritis, Rheumatoid / Q000188:drug therapy* / Q000378:metabolism*; D004351:Drug Resistance; D005260:Female; D005500:Follow-Up Studies; D005786:Gene Expression Regulation; D006801:Humans; D007166:Immunosuppressive Agents / Q000494:pharmacology; D008214:Lymphocytes / Q000378:metabolism; D008297:Male; D008727:Methotrexate / Q000494:pharmacology*; D008875:Middle Aged; D016896:Treatment Outcome
chemical_list: C513055:ABCB1 protein, human; D018435:ATP Binding Cassette Transporter, Subfamily B; D020168:ATP Binding Cassette Transporter, Subfamily B, Member 1; D007166:Immunosuppressive Agents; D008727:Methotrexate