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

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.

Exploring the Differences in Molecular Mechanisms and Key Biomarkers Between Membranous Nephropathy and Lupus Nephritis Using Integrated Bioinformatics Analysis

“…IFN-β produced by TLR3 or TLR4 stimulation can promote MX1 transcription ( Nistler et al, 2020 ). Expect for LN, MX1 up-regulation also exists in rheumatoid arthritis, idiopathic interstitial pneumonia, alopecia areata and other autoimmune diseases ( McDonagh and Tazi-Ahnini, 2002 ; Hamano et al, 2017 ; Yokoyama-Kokuryo et al, 2020 ). XAF1, also known as XIAP associated factor 1, plays an important role in cell apoptosis ( Jiang et al, 2018 ).…”

Interferon-induced protein with tetratricopeptide repeats 3 may be a key factor in primary biliary cholangitis

“…In the present study, we found for the first time the increased expression of IFIT3 relating to cellular senescence in BECs in PBC. Increased expression of IFIT3 and its association with pathophysiology were reported in several diseases such as SLE 27 , RA 28 and degenerative annulus fibrosus 29 . IFIT3 is an IFN-induced protein and upregulates cGMP-AMP synthase (cGAS)-signal via stimulator of IFN genes protein (STING) pathway 27 , 29 .…”

A comprehensive transcriptomic analysis of alternate interferon signaling pathways in peripheral blood mononuclear cells in rheumatoid arthritis

“…There were several imbalanced transcription factors in RA, such as IRF1 , IRF7 , STAT1 , and STAT2. They could be regulated by IFN, addressing the important IFN effects in RA [ 63 – 65 ]. Furthermore, we constructed GRNs by integrating the results of SCENIC analysis and DEG analysis in each cell type.…”