PMID- 32164778
OWN - NLM
STAT- MEDLINE
DCOM- 20210111
LR  - 20210111
IS  - 1478-6362 (Electronic)
IS  - 1478-6354 (Print)
IS  - 1478-6354 (Linking)
VI  - 22
IP  - 1
DP  - 2020 Mar 12
TI  - Identification of molecules associated with response to abatacept in patients 
      with rheumatoid arthritis.
PG  - 46
LID - 10.1186/s13075-020-2137-y [doi]
LID - 46
AB  - BACKGROUND: Abatacept (ABA) is a biological disease-modifying antirheumatic drug 
      (bDMARD) for rheumatoid arthritis (RA). The aim of this study was to identify 
      molecules that are associated with therapeutic responses to ABA in patients with 
      RA. METHODS: Peripheral blood was collected using a PAX gene Blood RNA kit from 
      45 bDMARD-naive patients with RA at baseline and at 6 months after the initiation 
      of ABA treatment. Gene expression levels of responders (n = 27) and 
      non-responders (n = 8) to ABA treatment among patients with RA at baseline were 
      compared using a microarray. The gene expression levels were confirmed using 
      real-time quantitative polymerase chain reaction (RT-qPCR). RESULTS: Gene 
      expression analysis revealed that the expression levels of 218 genes were 
      significantly higher and those of 392 genes were significantly lower in the 
      responders compared to the non-responders. Gene ontology analysis of the 218 
      genes identified "response to type I interferon (IFN)" with 24 type I IFN-related 
      genes. RT-qPCR confirmed that there was a strong correlation between the score 
      calculated using the 24 genes and that using OAS3, MX1, and IFIT3 (type I IFN 
      score) (rho with the type I IFN score 0.981); the type I IFN score was 
      significantly decreased after treatment with ABA in the responders (p < 0.05), 
      but not in the non-responders. The receiver operating characteristic curve 
      analysis of the type I IFN score showed that sensitivity, specificity, and AUC 
      (95% confidence interval) for the responders were 0.82, 1.00, and 0.92 
      (0.82-1.00), respectively. Further, RT-qPCR demonstrated higher expression levels 
      of BATF2, LAMP3, CD83, CLEC4A, IDO1, IRF7, STAT1, STAT2, and TNFSF10 in the 
      responders, all of which are dendritic cell-related genes or type I IFN-related 
      genes with significant biological implications. CONCLUSION: Type I IFN score and 
      expression levels of the nine genes may serve as novel biomarkers associated with 
      a clinical response to ABA in patients with RA.
FAU - Yokoyama-Kokuryo, Waka
AU  - Yokoyama-Kokuryo W
AD  - Department of Rheumatology, Tokyo Medical and Dental University, 1-5-45 Yushima, 
      Bunkyo-ku, Tokyo, 113-8519, Japan.
AD  - Department of Pharmacovigilance, Tokyo Medical and Dental University, 1-5-45 
      Yushima, Bunkyo-ku, Tokyo, 113-8519, Japan.
AD  - Department of Rheumatology, Japan Organization of Occupational Health and Safety 
      Chubu Rosai Hospital, 1-10-6 Koumei, Minato-ku, Nagoya-City, Aichi, Japan.
FAU - Yamazaki, Hayato
AU  - Yamazaki H
AD  - Department of Rheumatology, Tokyo Medical and Dental University, 1-5-45 Yushima, 
      Bunkyo-ku, Tokyo, 113-8519, Japan.
AD  - Department of Pharmacovigilance, Tokyo Medical and Dental University, 1-5-45 
      Yushima, Bunkyo-ku, Tokyo, 113-8519, Japan.
FAU - Takeuchi, Tsutomu
AU  - Takeuchi T
AD  - Division of Rheumatology, Department of Internal Medicine, Keio University School 
      of Medicine, 35 Shinanomachi, Shinjuku-ku, Tokyo, 160-8582, Japan.
FAU - Amano, Koichi
AU  - Amano K
AD  - Department of Rheumatology and Clinical Immunology, Saitama Medical Center, 
      Saitama Medical University, 1981 Kamoda, Kawagoe-shi, Saitama, 350-8550, Japan.
FAU - Kikuchi, Jun
AU  - Kikuchi J
AD  - Division of Rheumatology, Department of Internal Medicine, Keio University School 
      of Medicine, 35 Shinanomachi, Shinjuku-ku, Tokyo, 160-8582, Japan.
FAU - Kondo, Tsuneo
AU  - Kondo T
AD  - Department of Rheumatology and Clinical Immunology, Saitama Medical Center, 
      Saitama Medical University, 1981 Kamoda, Kawagoe-shi, Saitama, 350-8550, Japan.
FAU - Nakamura, Seiji
AU  - Nakamura S
AD  - DNA Chip Research Inc, 1-15-1 Kaigan, Minato-ku, Tokyo, 105-0022, Japan.
FAU - Sakai, Ryoko
AU  - Sakai R
AD  - Department of Pharmacovigilance, Tokyo Medical and Dental University, 1-5-45 
      Yushima, Bunkyo-ku, Tokyo, 113-8519, Japan.
AD  - Department of Rheumatology, Tokyo Women's Medical University School of Medicine, 
      8-1 Kawada-cho, Shinjuku-ku, Tokyo, 162-8666, Japan.
FAU - Hirano, Fumio
AU  - Hirano F
AD  - Department of Rheumatology, Tokyo Medical and Dental University, 1-5-45 Yushima, 
      Bunkyo-ku, Tokyo, 113-8519, Japan.
AD  - Department of Pharmacovigilance, Tokyo Medical and Dental University, 1-5-45 
      Yushima, Bunkyo-ku, Tokyo, 113-8519, Japan.
FAU - Nanki, Toshihiro
AU  - Nanki T
AD  - Department of Rheumatology, Tokyo Medical and Dental University, 1-5-45 Yushima, 
      Bunkyo-ku, Tokyo, 113-8519, Japan.
AD  - Department of Pharmacovigilance, Tokyo Medical and Dental University, 1-5-45 
      Yushima, Bunkyo-ku, Tokyo, 113-8519, Japan.
AD  - Division of Rheumatology, Department of Internal Medicine, Toho University School 
      of Medicine, 6-11-1 Omori-Nishi, Ota-ku, Tokyo, 143-8541, Japan.
FAU - Koike, Ryuji
AU  - Koike R
AD  - Department of Rheumatology, Tokyo Medical and Dental University, 1-5-45 Yushima, 
      Bunkyo-ku, Tokyo, 113-8519, Japan.
AD  - Department of Pharmacovigilance, Tokyo Medical and Dental University, 1-5-45 
      Yushima, Bunkyo-ku, Tokyo, 113-8519, Japan.
FAU - Harigai, Masayoshi
AU  - Harigai M
AUID- ORCID: 0000-0002-6418-2603
AD  - Department of Rheumatology, Tokyo Medical and Dental University, 1-5-45 Yushima, 
      Bunkyo-ku, Tokyo, 113-8519, Japan. harigai.masayoshi@twmu.ac.jp.
AD  - Department of Pharmacovigilance, Tokyo Medical and Dental University, 1-5-45 
      Yushima, Bunkyo-ku, Tokyo, 113-8519, Japan. harigai.masayoshi@twmu.ac.jp.
AD  - Department of Rheumatology, Tokyo Women's Medical University School of Medicine, 
      8-1 Kawada-cho, Shinjuku-ku, Tokyo, 162-8666, Japan. 
      harigai.masayoshi@twmu.ac.jp.
LA  - eng
GR  - #15K19570/Ministry of Health, Labour and Welfare/International
GR  - H30-meneki-shitei-002/Ministry of Health, Labour and Welfare/International
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
DEP - 20200312
PL  - England
TA  - Arthritis Res Ther
JT  - Arthritis research & therapy
JID - 101154438
RN  - 0 (Antirheumatic Agents)
RN  - 0 (Interferon Type I)
RN  - 7D0YB67S97 (Abatacept)
SB  - IM
MH  - Abatacept/*therapeutic use
MH  - Aged
MH  - Antirheumatic Agents/therapeutic use
MH  - Arthritis, Rheumatoid/diagnosis/*drug therapy/*genetics
MH  - Female
MH  - Humans
MH  - Interferon Type I/genetics/metabolism
MH  - Male
MH  - Middle Aged
MH  - Oligonucleotide Array Sequence Analysis/methods
MH  - ROC Curve
MH  - Reverse Transcriptase Polymerase Chain Reaction
MH  - Transcriptome/*genetics
MH  - Treatment Outcome
PMC - PMC7068901
OTO - NOTNLM
OT  - Abatacept
OT  - Interferon signature
OT  - Microarray
OT  - Prediction
OT  - Rheumatoid arthritis
COIS- WY-K received honoraria from Eisai Co., Ltd., Asahikasei Pharma Corp. HY is 
      currently an employee of Nippon Boehringer Ingelheim Co., Ltd. TT received Grants 
      from Astellas Pharma Inc., Chugai Pharmaceutical Co, Ltd., Daiichi Sankyo Co., 
      Ltd., Takeda Pharmaceutical Co., Ltd., AbbVie GK, Asahikasei Pharma Corp., 
      Mitsubishi Tanabe Pharma Co., Pfizer Japan Inc., Eisai Co., Ltd., AYUMI 
      Pharmaceutical Corporation, Nipponkayaku Co. Ltd., and Novartis Pharma K.K. TT 
      received personal fees from AbbVie GK., Astellas Pharma Inc., Astra Zeneca K.K., 
      Bristol-Myers K.K., Chugai Pharmaceutical Co. Ltd., Diaichi Sankyo Co. Ltd., 
      Eisai Co. Ltd., Eli Lilly Japan K.K., GlaxoSmithKline K.K., Janssen 
      Pharmaceutical K.K., Mitsubishi Tanabe Pharma Co., Nipponkayaku Co., Ltd., 
      Novartis Pharma K.K., Pfizer Japan Inc., Sanofi K.K., Teijin Pharma Ltd., Taiho 
      Pharmaceutical Co. Ltd., Taisho Pharmaceutical Co. Ltd., Takeda Pharmaceutical 
      Co. Ltd., and UCB Japan Co. Ltd. KA received honoraria from Chugai Pharmaceutical 
      Co. Ltd., Eli Lilly Japan K.K., Pfizer Japan Inc., and Mitsubishi Tanabe Pharma 
      and the research grant from Chugai Pharmaceutical Co. Ltd. and Asahi Kasei 
      Pharma. JK received honoraria from Astellas Pharma Inc., Chugai Pharmaceutical 
      Co., Ltd., Mitsubishi Tanabe Pharma Co., Pfizer Japan Inc., Eisai Co., Ltd., 
      Bristol-Myers K.K., Eli Lilly Japan K.K., GlaxoSmithKline K.K., Janssen 
      Pharmaceutical K.K., and Sanofi K.K. Tokyo Medical and Dental University (TMDU) 
      received unrestricted research grants for Department of Pharmacovigilance from 
      AbbVie Japan Co., Ltd., Astellas Pharma Inc., Bristol-Myers Squibb K.K., Chugai 
      Pharmaceutical Co., Ltd., Eisai Co., Ltd., Mitsubishi Tanabe Pharma Co., Ono 
      Pharmaceuticals, Pfizer Japan Inc., Sanofi-Aventis K.K., Santen Pharmaceutical 
      Co., Ltd., Takeda Pharmaceutical Co., Ltd., and UCB Japan, with which TMDU paid 
      the salaries of HY, RS, TN, and MH. The Department of Lifetime Clinical 
      Immunology of Tokyo Medical and Dental University (TMDU) has received 
      unrestricted research grants from Chugai Pharmaceutical Co., Ltd.; Ono 
      Pharmaceuticals; Mitsubishi Tanabe Pharma Co.; UCB Japan; CSL Behring; Towa 
      Pharmaceutical Co., Ltd.; Abbvie Japan Co., Ltd.; Japan Blood Products 
      Organization; Ayumi Pharmaceutical Co.; and Nippon Kayaku Co., Ltd., with which 
      TMDU currently pays the salary of FH. FH also received consulting fees from Ono 
      Pharmaceuticals, Astellas Pharma Inc., Sumitomo Dainippon Pharma, and Chugai 
      Pharmaceutical Co., Ltd. SN, TK, and RK have nothing to declare.
EDAT- 2020/03/14 06:00
MHDA- 2021/01/12 06:00
PMCR- 2020/03/12
CRDT- 2020/03/14 06:00
PHST- 2019/08/26 00:00 [received]
PHST- 2020/02/21 00:00 [accepted]
PHST- 2020/03/14 06:00 [entrez]
PHST- 2020/03/14 06:00 [pubmed]
PHST- 2021/01/12 06:00 [medline]
PHST- 2020/03/12 00:00 [pmc-release]
AID - 10.1186/s13075-020-2137-y [pii]
AID - 2137 [pii]
AID - 10.1186/s13075-020-2137-y [doi]
PST - epublish
SO  - Arthritis Res Ther. 2020 Mar 12;22(1):46. doi: 10.1186/s13075-020-2137-y.