Multidrug Resistant Lymphocytes of Patients with Rheumatoid Arthritis Are Predictive for DMARD and Glucocorticoid Treatment Response

Jan Piet van Hamburg¹, Sandra M.J. Paulissen², Nadine Davelaar¹, Mieke Hazes³ and Erik Lubberts¹, ¹Rheumatology and Immunology, Erasmus MC, University Medical Center Rotterdam, Rotterdam, Netherlands, ²Room Nb-84, Erasmus MC, University Medical Center Rotterdam, Rotterdam, Netherlands, ³Rheumatology, Erasmus MC, University Medical Center Rotterdam, Rotterdam, Netherlands

Meeting: 2015 ACR/ARHP Annual Meeting

Date of first publication: September 29, 2015

Keywords: glucocorticoids, lymphocytes, methotrexate (MTX) and rheumatoid arthritis (RA)

Session Information

Date: Sunday, November 8, 2015

Title: Rheumatoid Arthritis - Human Etiology and Pathogenesis Poster I

Session Type: ACR Poster Session A

Session Time: 9:00AM-11:00AM

Background/Purpose: A large fraction of patients with RA does not respond to treatment with glucocorticoids (GCs) and disease-modifying anti-rheumatic drugs (DMARDs), or becomes resistant in time. Multidrug resistance may underlie the lack of response, but markers to predict or monitor drug resistance in RA are lacking. In this study, drug efflux capacity and multidrug transporter expression were investigated on various lymphocyte populations in relation to combined DMARD/GC therapy response.

Methods: Peripheral and/or synovial lymphocytes were obtained from: healthy individuals, established inflammatory arthritis patients and DMARD/GC therapy responders and non-responders at baseline and after 6 months of therapy. Drug efflux capacity, indicated by rhodamine-123 (Rh123) and calcein transport, and MDR1, MRP1 and ABCG2 expression were analysed for total lymphocytes, as well as for B, CD4+ T, CD8+ T and natural killer (NK) cells.

Results: Compared to healthy individuals, lymphocytes from patients with inflammatory arthritis showed a higher drug efflux capacity and expressed higher MDR1 and MRP1 levels. DMARD/GC non-response was associated with lower MDR1 expression and Rh123 efflux by naïve CD8+ T cells at baseline and increased MRP1 expression and calcein efflux after 6 months of treatment. Blocking MRP1 activity partially inhibited calcein efflux by peripheral and synovial lymphocytes, indicating additional MRP1-independent drug resistance.

Conclusion: Multidrug resistant lymphocytes are present in RA. In addition, MDR1 expression and activity in naïve CD8+ T cells was identified as a marker to distinguish DMARD/GC therapy responders from non-responders at baseline. Moreover, increased calcein efflux capacity by lymphocytes during DMARD/GC treatment is associated with the lack of response on this treatment. Implementation of these findings in current diagnostic and treatment protocols might lead to improved personalized RA treatment strategies.

Disclosure: J. P. van Hamburg, None; S. M. J. Paulissen, None; N. Davelaar, None; M. Hazes, None; E. Lubberts, None.

To cite this abstract in AMA style:

van Hamburg JP, Paulissen SMJ, Davelaar N, Hazes M, Lubberts E. Multidrug Resistant Lymphocytes of Patients with Rheumatoid Arthritis Are Predictive for DMARD and Glucocorticoid Treatment Response [abstract]. Arthritis Rheumatol. 2015; 67 (suppl 10). https://acrabstracts.org/abstract/multidrug-resistant-lymphocytes-of-patients-with-rheumatoid-arthritis-are-predictive-for-dmard-and-glucocorticoid-treatment-response/. Accessed .

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