PMID- 30709954
OWN - NLM
STAT- Publisher
LR  - 20190302
IS  - 0315-162X (Print)
IS  - 0315-162X (Linking)
DP  - 2019 Feb 1
TI  - Peripheral Lymphocyte Multidrug Resistance Activity as a Predictive Tool of
      Biological Therapeutic Response in Rheumatoid Arthritis.
LID - jrheum.180793 [pii]
LID - 10.3899/jrheum.180793 [doi]
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.
FAU - Toldi, Gergely
AU  - Toldi G
AUID- ORCID: https://orcid.org/0000-0003-0178-1243
AD  - 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. Barath, MD, PhD,
      Department of Laboratory Medicine, University of Debrecen; P. Szeremy, MSc,
      MDQuest Ltd.; A. Apjok, MD, MDQuest Ltd.; K. Filkor, PhD, MDQuest Ltd.; S.
      Szanto, MD, DSc, Third Department of Internal Medicine, University of Debrecen;
      G. Szucs, MD, DSc, Third Department of Internal Medicine, University of Debrecen;
      S. Szamosi, MD, PhD, Third Department of Internal Medicine, University of
      Debrecen; T. Haupl, MD, PhD, DRFZ; A. Grutzkau, PhD, DRFZ; Z. Szekanecz, MD, DSc,
      Third Department of Internal Medicine, University of Debrecen. Address
      correspondence to Dr. G. Toldi, MDQuest Ltd., Kozep fasor 52, Szeged, H-6726,
      Hungary. E-mail: toldi@mdquest.hu. Accepted for publication November 8, 2018.
FAU - Batel, Patrizia
AU  - Batel P
AD  - 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. Barath, MD, PhD,
      Department of Laboratory Medicine, University of Debrecen; P. Szeremy, MSc,
      MDQuest Ltd.; A. Apjok, MD, MDQuest Ltd.; K. Filkor, PhD, MDQuest Ltd.; S.
      Szanto, MD, DSc, Third Department of Internal Medicine, University of Debrecen;
      G. Szucs, MD, DSc, Third Department of Internal Medicine, University of Debrecen;
      S. Szamosi, MD, PhD, Third Department of Internal Medicine, University of
      Debrecen; T. Haupl, MD, PhD, DRFZ; A. Grutzkau, PhD, DRFZ; Z. Szekanecz, MD, DSc,
      Third Department of Internal Medicine, University of Debrecen. Address
      correspondence to Dr. G. Toldi, MDQuest Ltd., Kozep fasor 52, Szeged, H-6726,
      Hungary. E-mail: toldi@mdquest.hu. Accepted for publication November 8, 2018.
FAU - Barath, Sandor
AU  - Barath S
AD  - 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. Barath, MD, PhD,
      Department of Laboratory Medicine, University of Debrecen; P. Szeremy, MSc,
      MDQuest Ltd.; A. Apjok, MD, MDQuest Ltd.; K. Filkor, PhD, MDQuest Ltd.; S.
      Szanto, MD, DSc, Third Department of Internal Medicine, University of Debrecen;
      G. Szucs, MD, DSc, Third Department of Internal Medicine, University of Debrecen;
      S. Szamosi, MD, PhD, Third Department of Internal Medicine, University of
      Debrecen; T. Haupl, MD, PhD, DRFZ; A. Grutzkau, PhD, DRFZ; Z. Szekanecz, MD, DSc,
      Third Department of Internal Medicine, University of Debrecen. Address
      correspondence to Dr. G. Toldi, MDQuest Ltd., Kozep fasor 52, Szeged, H-6726,
      Hungary. E-mail: toldi@mdquest.hu. Accepted for publication November 8, 2018.
FAU - Szeremy, Peter
AU  - Szeremy P
AD  - 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. Barath, MD, PhD,
      Department of Laboratory Medicine, University of Debrecen; P. Szeremy, MSc,
      MDQuest Ltd.; A. Apjok, MD, MDQuest Ltd.; K. Filkor, PhD, MDQuest Ltd.; S.
      Szanto, MD, DSc, Third Department of Internal Medicine, University of Debrecen;
      G. Szucs, MD, DSc, Third Department of Internal Medicine, University of Debrecen;
      S. Szamosi, MD, PhD, Third Department of Internal Medicine, University of
      Debrecen; T. Haupl, MD, PhD, DRFZ; A. Grutzkau, PhD, DRFZ; Z. Szekanecz, MD, DSc,
      Third Department of Internal Medicine, University of Debrecen. Address
      correspondence to Dr. G. Toldi, MDQuest Ltd., Kozep fasor 52, Szeged, H-6726,
      Hungary. E-mail: toldi@mdquest.hu. Accepted for publication November 8, 2018.
FAU - Apjok, Andras
AU  - Apjok A
AD  - 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. Barath, MD, PhD,
      Department of Laboratory Medicine, University of Debrecen; P. Szeremy, MSc,
      MDQuest Ltd.; A. Apjok, MD, MDQuest Ltd.; K. Filkor, PhD, MDQuest Ltd.; S.
      Szanto, MD, DSc, Third Department of Internal Medicine, University of Debrecen;
      G. Szucs, MD, DSc, Third Department of Internal Medicine, University of Debrecen;
      S. Szamosi, MD, PhD, Third Department of Internal Medicine, University of
      Debrecen; T. Haupl, MD, PhD, DRFZ; A. Grutzkau, PhD, DRFZ; Z. Szekanecz, MD, DSc,
      Third Department of Internal Medicine, University of Debrecen. Address
      correspondence to Dr. G. Toldi, MDQuest Ltd., Kozep fasor 52, Szeged, H-6726,
      Hungary. E-mail: toldi@mdquest.hu. Accepted for publication November 8, 2018.
FAU - Filkor, Kata
AU  - Filkor K
AD  - 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. Barath, MD, PhD,
      Department of Laboratory Medicine, University of Debrecen; P. Szeremy, MSc,
      MDQuest Ltd.; A. Apjok, MD, MDQuest Ltd.; K. Filkor, PhD, MDQuest Ltd.; S.
      Szanto, MD, DSc, Third Department of Internal Medicine, University of Debrecen;
      G. Szucs, MD, DSc, Third Department of Internal Medicine, University of Debrecen;
      S. Szamosi, MD, PhD, Third Department of Internal Medicine, University of
      Debrecen; T. Haupl, MD, PhD, DRFZ; A. Grutzkau, PhD, DRFZ; Z. Szekanecz, MD, DSc,
      Third Department of Internal Medicine, University of Debrecen. Address
      correspondence to Dr. G. Toldi, MDQuest Ltd., Kozep fasor 52, Szeged, H-6726,
      Hungary. E-mail: toldi@mdquest.hu. Accepted for publication November 8, 2018.
FAU - Szanto, Sandor
AU  - Szanto S
AD  - 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. Barath, MD, PhD,
      Department of Laboratory Medicine, University of Debrecen; P. Szeremy, MSc,
      MDQuest Ltd.; A. Apjok, MD, MDQuest Ltd.; K. Filkor, PhD, MDQuest Ltd.; S.
      Szanto, MD, DSc, Third Department of Internal Medicine, University of Debrecen;
      G. Szucs, MD, DSc, Third Department of Internal Medicine, University of Debrecen;
      S. Szamosi, MD, PhD, Third Department of Internal Medicine, University of
      Debrecen; T. Haupl, MD, PhD, DRFZ; A. Grutzkau, PhD, DRFZ; Z. Szekanecz, MD, DSc,
      Third Department of Internal Medicine, University of Debrecen. Address
      correspondence to Dr. G. Toldi, MDQuest Ltd., Kozep fasor 52, Szeged, H-6726,
      Hungary. E-mail: toldi@mdquest.hu. Accepted for publication November 8, 2018.
FAU - Szucs, Gabriella
AU  - Szucs G
AUID- ORCID: http://orcid.org/0000-0002-0958-9531
AD  - 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. Barath, MD, PhD,
      Department of Laboratory Medicine, University of Debrecen; P. Szeremy, MSc,
      MDQuest Ltd.; A. Apjok, MD, MDQuest Ltd.; K. Filkor, PhD, MDQuest Ltd.; S.
      Szanto, MD, DSc, Third Department of Internal Medicine, University of Debrecen;
      G. Szucs, MD, DSc, Third Department of Internal Medicine, University of Debrecen;
      S. Szamosi, MD, PhD, Third Department of Internal Medicine, University of
      Debrecen; T. Haupl, MD, PhD, DRFZ; A. Grutzkau, PhD, DRFZ; Z. Szekanecz, MD, DSc,
      Third Department of Internal Medicine, University of Debrecen. Address
      correspondence to Dr. G. Toldi, MDQuest Ltd., Kozep fasor 52, Szeged, H-6726,
      Hungary. E-mail: toldi@mdquest.hu. Accepted for publication November 8, 2018.
FAU - Szamosi, Szilvia
AU  - Szamosi S
AD  - 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. Barath, MD, PhD,
      Department of Laboratory Medicine, University of Debrecen; P. Szeremy, MSc,
      MDQuest Ltd.; A. Apjok, MD, MDQuest Ltd.; K. Filkor, PhD, MDQuest Ltd.; S.
      Szanto, MD, DSc, Third Department of Internal Medicine, University of Debrecen;
      G. Szucs, MD, DSc, Third Department of Internal Medicine, University of Debrecen;
      S. Szamosi, MD, PhD, Third Department of Internal Medicine, University of
      Debrecen; T. Haupl, MD, PhD, DRFZ; A. Grutzkau, PhD, DRFZ; Z. Szekanecz, MD, DSc,
      Third Department of Internal Medicine, University of Debrecen. Address
      correspondence to Dr. G. Toldi, MDQuest Ltd., Kozep fasor 52, Szeged, H-6726,
      Hungary. E-mail: toldi@mdquest.hu. Accepted for publication November 8, 2018.
FAU - Haupl, Thomas
AU  - Haupl T
AD  - 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. Barath, MD, PhD,
      Department of Laboratory Medicine, University of Debrecen; P. Szeremy, MSc,
      MDQuest Ltd.; A. Apjok, MD, MDQuest Ltd.; K. Filkor, PhD, MDQuest Ltd.; S.
      Szanto, MD, DSc, Third Department of Internal Medicine, University of Debrecen;
      G. Szucs, MD, DSc, Third Department of Internal Medicine, University of Debrecen;
      S. Szamosi, MD, PhD, Third Department of Internal Medicine, University of
      Debrecen; T. Haupl, MD, PhD, DRFZ; A. Grutzkau, PhD, DRFZ; Z. Szekanecz, MD, DSc,
      Third Department of Internal Medicine, University of Debrecen. Address
      correspondence to Dr. G. Toldi, MDQuest Ltd., Kozep fasor 52, Szeged, H-6726,
      Hungary. E-mail: toldi@mdquest.hu. Accepted for publication November 8, 2018.
FAU - Grutzkau, Andreas
AU  - Grutzkau A
AD  - 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. Barath, MD, PhD,
      Department of Laboratory Medicine, University of Debrecen; P. Szeremy, MSc,
      MDQuest Ltd.; A. Apjok, MD, MDQuest Ltd.; K. Filkor, PhD, MDQuest Ltd.; S.
      Szanto, MD, DSc, Third Department of Internal Medicine, University of Debrecen;
      G. Szucs, MD, DSc, Third Department of Internal Medicine, University of Debrecen;
      S. Szamosi, MD, PhD, Third Department of Internal Medicine, University of
      Debrecen; T. Haupl, MD, PhD, DRFZ; A. Grutzkau, PhD, DRFZ; Z. Szekanecz, MD, DSc,
      Third Department of Internal Medicine, University of Debrecen. Address
      correspondence to Dr. G. Toldi, MDQuest Ltd., Kozep fasor 52, Szeged, H-6726,
      Hungary. E-mail: toldi@mdquest.hu. Accepted for publication November 8, 2018.
FAU - Szekanecz, Zoltan
AU  - Szekanecz Z
AD  - 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. Barath, MD, PhD,
      Department of Laboratory Medicine, University of Debrecen; P. Szeremy, MSc,
      MDQuest Ltd.; A. Apjok, MD, MDQuest Ltd.; K. Filkor, PhD, MDQuest Ltd.; S.
      Szanto, MD, DSc, Third Department of Internal Medicine, University of Debrecen;
      G. Szucs, MD, DSc, Third Department of Internal Medicine, University of Debrecen;
      S. Szamosi, MD, PhD, Third Department of Internal Medicine, University of
      Debrecen; T. Haupl, MD, PhD, DRFZ; A. Grutzkau, PhD, DRFZ; Z. Szekanecz, MD, DSc,
      Third Department of Internal Medicine, University of Debrecen. Address
      correspondence to Dr. G. Toldi, MDQuest Ltd., Kozep fasor 52, Szeged, H-6726,
      Hungary. E-mail: toldi@mdquest.hu. Accepted for publication November 8, 2018.
LA  - eng
PT  - Journal Article
DEP - 20190201
PL  - Canada
TA  - J Rheumatol
JT  - The Journal of rheumatology
JID - 7501984
EDAT- 2019/02/03 06:00
MHDA- 2019/02/03 06:00
CRDT- 2019/02/03 06:00
PHST- 2019/02/03 06:00 [pubmed]
PHST- 2019/02/03 06:00 [medline]
PHST- 2019/02/03 06:00 [entrez]
AID - jrheum.180793 [pii]
AID - 10.3899/jrheum.180793 [doi]
PST - aheadofprint
SO  - J Rheumatol. 2019 Feb 1. pii: jrheum.180793. doi: 10.3899/jrheum.180793.