Multidrug resistance protein-1 expression, function and polymorphisms in patients with rheumatoid arthritis not responding to methotrexate

Objective: To study the expression, function and polymorphism of MDR-1 protein on the peripheral blood lymphocytes in patients with RA following treatment with MTX and its relationship with response to therapy.

Methods: RA patients naïve to MTX/DMARD- and glucocorticoid were enrolled. Expression and function of MDR-1 was carried out by flow cytometry at baseline and after 4 months of therapy. MDR-1 expression was measured by relative fluorescence intensities and percentage of positive cells. MDR-1 function was assessed by Rhodamine efflux in presence or absence of verapamil. Patients with reduction in disease activity score 28 ≥1.2 were defined as responders and <1.2 as non-responders. Three single nucleotide polymorphisms in MDR-1 gene, 3435T, 1236T and 2677T/A were studied.

Results: Fifty-two patients of RA were grouped into responders (n = 41), and non-responders (n = 11) as per the defined criteria. There was no difference between the groups in terms of age, sex ratio or duration of illness, MTX dose and follow-up duration. The expression and function of the MDR-1 protein reduced significantly in the responder group after the treatment with MTX when compared to the baseline evaluation. The decrease was significant when compared to the non-responders at the fourth month. MDR-1 expression and function either increased or remained the same in the non-responder group after treatment with MTX. MTX unresponsiveness was not related to any of the three polymorphisms studied.

Conclusion: Persistent expression and function of MDR-1 identifies a subset of RA patients not responding to MTX. Its early recognition may help in appropriately modulating therapy.