Abstract | BACKGROUND: 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.
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Authors | 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 |
Journal | Arthritis research & therapy
(Arthritis Res Ther)
Vol. 22
Issue 1
Pg. 46
(03 12 2020)
ISSN: 1478-6362 [Electronic] England |
PMID | 32164778
(Publication Type: Journal Article, Research Support, Non-U.S. Gov't)
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Chemical References |
- Antirheumatic Agents
- Interferon Type I
- Abatacept
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Topics |
- Abatacept
(therapeutic use)
- Aged
- Antirheumatic Agents
(therapeutic use)
- Arthritis, Rheumatoid
(diagnosis, drug therapy, genetics)
- Female
- Humans
- Interferon Type I
(genetics, metabolism)
- Male
- Middle Aged
- Oligonucleotide Array Sequence Analysis
(methods)
- ROC Curve
- Reverse Transcriptase Polymerase Chain Reaction
- Transcriptome
(genetics)
- Treatment Outcome
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