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J Rheumatol. 2019 Feb 1. pii: jrheum.180793. doi: 10.3899/jrheum.180793. [Epub ahead of print]

Peripheral Lymphocyte Multidrug Resistance Activity as a Predictive Tool of Biological Therapeutic Response in Rheumatoid Arthritis.

Author information

1
From the MDQuest Ltd., Szeged, Hungary; German Rheumatism Research Centre Berlin (DRFZ), an Institute of the Leibniz Association, Berlin, Germany; Department of Laboratory Medicine, University of Debrecen, Third Department of Internal Medicine, University of Debrecen, Debrecen, Hungary. KF is employed by MDQuest Ltd. G. Toldi, MD, PhD, MDQuest Ltd.; P. Batel, MSc, DRFZ; S. Baráth, MD, PhD, Department of Laboratory Medicine, University of Debrecen; P. Szerémy, MSc, MDQuest Ltd.; A. Apjok, MD, MDQuest Ltd.; K. Filkor, PhD, MDQuest Ltd.; S. Szántó, MD, DSc, Third Department of Internal Medicine, University of Debrecen; G. Szűcs, MD, DSc, Third Department of Internal Medicine, University of Debrecen; S. Szamosi, MD, PhD, Third Department of Internal Medicine, University of Debrecen; T. Häupl, MD, PhD, DRFZ; A. Grützkau, PhD, DRFZ; Z. Szekanecz, MD, DSc, Third Department of Internal Medicine, University of Debrecen. Address correspondence to Dr. G. Toldi, MDQuest Ltd., Közép fasor 52, Szeged, H-6726, Hungary. E-mail: toldi@mdquest.hu. Accepted for publication November 8, 2018.

Abstract

OBJECTIVE:

Multidrug resistance (MDR) transporters may be used as biomarkers to monitor disease progression in RA and as a predictive tool to establish responsiveness to biological therapy. In this multicenter clinical trial, we aimed to assess the predictive value of activity measurement of transporters MDR1, MD resistance protein (MRP)1, and breast cancer resistance protein (BCRP) for biological therapeutic response in RA before the initiation of biological therapy as well as 4 to 6 and 12 weeks after.

METHODS:

Peripheral blood samples were collected from 27 responders and 12 nonresponders to biological disease-modifying antirheumatic drugs (bDMARD) at the indicated timepoints as well as from 35 healthy controls. MDR activity factor (MAF) of MDR1, MRP1, and BCRP was measured in CD3+ and CD19+ cells using the Solvo MDQ Kit and cell surface staining by flow cytometry following peripheral blood mononuclear cells isolation.

RESULTS:

At the start of therapy, MAFC (composite MAF of MRP1 and MDR1) and MAFMDR values, and at 4 to 6 weeks of treatment, MAFC, MAFMRP, and MAFMDR values of CD3 cells were higher in nonresponders compared to responders. Receiver-operation characteristic curve analysis revealed that RA patients with MAFC values above 21.3 in CD3 cells at the start of bDMARD therapy are likely to be nonresponders. At 4 to 6 weeks of treatment, these also predict unfavorable response: MAFC values above 20.3, MAFMRP values above 6.0, and MAFMDR values above 13.9 in CD3 cells.

CONCLUSION:

Our results indicate that the determination of MAFC values in CD3 cells of patients with RA may be of predictive value prior to the initiation of biological therapy, to establish whether the patient will demonstrate sufficient therapeutic response.

PMID:
30709954
DOI:
10.3899/jrheum.180793

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