Peripheral lymphocyte multidrug resistance activity as a predictive tool of biological therapeutic response in rheumatoid arthritis

Gergely Toldi, Patrizia Batel, S. Baráth, Péter Szerémy, András Apjok, Kata Filkor, S. Szántó, G. Szűcs, Szilvia Szamosi, Thomas Häupl, Andreas Grützkau, Z. Szekanecz

Research output: Contribution to journalArticle

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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.

Original languageEnglish
Pages (from-to)572-578
Number of pages7
JournalJournal of Rheumatology
Volume46
Issue number6
DOIs
Publication statusPublished - Jan 1 2019

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Multiple Drug Resistance
Rheumatoid Arthritis
Lymphocytes
Biological Therapy
Antirheumatic Agents
Therapeutics
BRCA1 Protein
Cell Separation
R Factors
Multicenter Studies
Disease Progression
Blood Cells
Flow Cytometry
Proteins
Biomarkers
Clinical Trials
Staining and Labeling
Breast Neoplasms
Drug Therapy

Keywords

  • Multidrug Resistance
  • Rheumatoid Arthritis
  • T Cells
  • Therapeutic Response

ASJC Scopus subject areas

  • Rheumatology
  • Immunology and Allergy
  • Immunology

Cite this

Peripheral lymphocyte multidrug resistance activity as a predictive tool of biological therapeutic response in rheumatoid arthritis. / Toldi, Gergely; Batel, Patrizia; Baráth, S.; Szerémy, Péter; Apjok, András; Filkor, Kata; Szántó, S.; Szűcs, G.; Szamosi, Szilvia; Häupl, Thomas; Grützkau, Andreas; Szekanecz, Z.

In: Journal of Rheumatology, Vol. 46, No. 6, 01.01.2019, p. 572-578.

Research output: Contribution to journalArticle

Toldi, Gergely ; Batel, Patrizia ; Baráth, S. ; Szerémy, Péter ; Apjok, András ; Filkor, Kata ; Szántó, S. ; Szűcs, G. ; Szamosi, Szilvia ; Häupl, Thomas ; Grützkau, Andreas ; Szekanecz, Z. / Peripheral lymphocyte multidrug resistance activity as a predictive tool of biological therapeutic response in rheumatoid arthritis. In: Journal of Rheumatology. 2019 ; Vol. 46, No. 6. pp. 572-578.
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AU - Batel, Patrizia

AU - Baráth, S.

AU - Szerémy, Péter

AU - Apjok, András

AU - Filkor, Kata

AU - Szántó, S.

AU - Szűcs, G.

AU - Szamosi, Szilvia

AU - Häupl, Thomas

AU - Grützkau, Andreas

AU - Szekanecz, Z.

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AB - 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.

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