Identification of molecules associated with response to abatacept in patients with rheumatoid arthritis

Waka Yokoyama-Kokuryo, Hayato Yamazaki, Tsutomu Takeuchi, Koichi Amano, Jun Kikuchi, Tsuneo Kondo, Seiji Nakamura, Ryoko Sakai, Fumio Hirano, Toshihiro Nanki, Ryuji Koike, Masayoshi Harigai

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Abstract

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-naïve 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.

Original languageEnglish
Article number46
JournalArthritis Research and Therapy
Volume22
Issue number1
DOIs
Publication statusPublished - 2020 Mar 12

Keywords

  • Abatacept
  • Interferon signature
  • Microarray
  • Prediction
  • Rheumatoid arthritis

ASJC Scopus subject areas

  • Rheumatology
  • Immunology and Allergy
  • Immunology

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    Yokoyama-Kokuryo, W., Yamazaki, H., Takeuchi, T., Amano, K., Kikuchi, J., Kondo, T., Nakamura, S., Sakai, R., Hirano, F., Nanki, T., Koike, R., & Harigai, M. (2020). Identification of molecules associated with response to abatacept in patients with rheumatoid arthritis. Arthritis Research and Therapy, 22(1), [46]. https://doi.org/10.1186/s13075-020-2137-y