Distinct single cell gene expression in peripheral blood monocytes correlates with treatment response groups defined by type I interferon in rheumatoid arthritis
Distinct single cell gene expression in peripheral blood monocytes correlates with treatment response groups defined by type I interferon in rheumatoid arthritis
Abstract ObjectivePreviously, we have shown that the ratio of IFNβ/α activity can predict response to tumor necrosis factor inhibitors (TNFi) in rheumatoid arthritis (RA). In this study, our objective was to better understand the impact of this type I IFN ratio in monocytes from RA patients. MethodsWe compared single cell gene expression in purified classical (CL) and non-classical (NC) monocytes from RA patients. Patients with high vs. low serum IFNβ/α ratio were compared to each other, as determined by functional type I IFN assay. ResultsWe found large differences in monocyte gene expression between patients with different IFNβ/α ratios, which was apparent in principal component analysis. Cluster analysis also documented strong differences between these response groups. In CL monocytes, decreased expression of JAK1 and IFI27 were strongly associated with the non-response low IFNβ/α ratio. In NC monocytes, increased expression of HLADRB1, TNFA, PDL1, TGFB, and others were associated with the non-response IFN ratio. Interestingly, JAK1 expression was absent in all monocytes from some patients. This pattern was strongly associated with the non-response type I IFN ratio, suggesting a major biological difference between JAK1 expressors and non-expressors. ConclusionsDifferences in the ratio of IFNβ/α are associated with major changes in gene expression in RA patient monocytes, suggesting differential IFN pathway activation in RA patients who are either more or less likely to respond to TNFi. This work could suggest mechanisms for TNFi non-response, as well as potential therapeutic strategies for those patients who would not to respond to TNFi.
Jin Zhongbo、Jensen Mark A.、Dorschner Jessica M.、Dicke Betty、Davis John M.、Persellin Scott、Matteson Eric、Vsetecka Danielle、Wright Kerry、Mason Thomas、Niewold Timothy B.、Fan Wei、Wampler Muskardin Theresa L.、Michet Clement J.、Ghodke-Puranik Yogita
Department of Pathology, Immunology and Laboratory Medicine, University of Florida College of MedicineColton Center for Autoimmunity ¨C Department of Medicine, New York University School of Medicine||Division of Rheumatology - Department of Medicine, New York University School of MedicineDepartment of Internal Medicine, Division of Rheumatology, Mayo ClinicDepartment of Internal Medicine, Division of Rheumatology, Mayo ClinicDepartment of Internal Medicine, Division of Rheumatology, Mayo ClinicDepartment of Internal Medicine, Division of Rheumatology, Mayo ClinicDepartment of Internal Medicine, Division of Rheumatology, Mayo ClinicUnitedHealth Group, Research & DevelopmentDepartment of Internal Medicine, Division of Rheumatology, Mayo ClinicDepartment of Internal Medicine, Division of Rheumatology, Mayo ClinicColton Center for Autoimmunity ¨C Department of Medicine, New York University School of MedicineDepartment of Rheumatology, Ren Ji Hospital, School of Medicine, Shanghai Jiao Tong UniversityColton Center for Autoimmunity ¨C Department of Medicine, New York University School of Medicine||Division of Rheumatology - Department of Medicine, New York University School of MedicineDepartment of Internal Medicine, Division of Rheumatology, Mayo ClinicColton Center for Autoimmunity ¨C Department of Medicine, New York University School of Medicine||Division of Rheumatology - Department of Medicine, New York University School of Medicine
基础医学细胞生物学分子生物学
Jin Zhongbo,Jensen Mark A.,Dorschner Jessica M.,Dicke Betty,Davis John M.,Persellin Scott,Matteson Eric,Vsetecka Danielle,Wright Kerry,Mason Thomas,Niewold Timothy B.,Fan Wei,Wampler Muskardin Theresa L.,Michet Clement J.,Ghodke-Puranik Yogita.Distinct single cell gene expression in peripheral blood monocytes correlates with treatment response groups defined by type I interferon in rheumatoid arthritis[EB/OL].(2025-03-28)[2025-05-02].https://www.medrxiv.org/content/10.1101/19011460.点此复制
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