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This study was undertaken to investigate Pim\u20101 and its family members as potential therapeutic targets in early rheumatoid arthritis (RA).<\/jats:p><\/jats:sec><jats:sec><jats:title>Methods<\/jats:title><jats:p>A flow cytometry assay for <jats:italic>PIM1<\/jats:italic> transcript measurement in peripheral blood mononuclear cells from patients with early arthritis was validated and applied as a biomarker of Pim\u20101 activity at the cellular level. Synovial protein expression was similarly determined by multiplex immunofluorescence in tissue samples from untreated RA patients and non\u2010RA disease controls. Functional consequences of Pim kinase family manipulation in freshly isolated CD4+ T cells from these individuals were ascertained, along with the impact of Pim inhibition on mice with collagen\u2010induced arthritis (CIA).<\/jats:p><\/jats:sec><jats:sec><jats:title>Results<\/jats:title><jats:p>The percentage of circulating CD4+ T cells positive for <jats:italic>PIM1<\/jats:italic> transcript by flow cytometry proved a faithful surrogate for gene expression and was significantly higher in patients with early RA than in those with other diseases. Pim\u20101 protein levels were similarly up\u2010regulated in synovial CD4+ T cells from patients with early RA. Ex vivo, exposure of T cell receptor\u2013stimulated early RA CD4+ T cells to Pim kinase inhibitors restrained their activation and proliferative capacity. Diminished production of proinflammatory cytokines (interferon\u2010\u03b3 and interleukin\u201017) and an expanded CD25<jats:sup>high<\/jats:sup>FoxP3+ Treg cell fraction were also observed in exposed versus unexposed cells. Finally, administration of Pim inhibitors robustly limited arthritis progression and cartilage destruction in CIA.<\/jats:p><\/jats:sec><jats:sec><jats:title>Conclusion<\/jats:title><jats:p>Our findings indicate that Pim kinases are plausible therapeutic targets in a readily identifiable subgroup of patients with early RA. Repurposing of Pim inhibitors for this disease should be considered.<\/jats:p><\/jats:sec>","DOI":"10.1002\/art.41744","type":"journal-article","created":{"date-parts":[[2021,3,29]],"date-time":"2021-03-29T01:45:48Z","timestamp":1616982348000},"page":"1820-1830","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":30,"title":["Pim Kinases as Therapeutic Targets in Early Rheumatoid\u00a0Arthritis"],"prefix":"10.1002","volume":"73","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-6079-2914","authenticated-orcid":false,"given":"Nicola J.","family":"Maney","sequence":"first","affiliation":[{"name":"Newcastle University Translational and Clinical Research Institute Newcastle University  Newcastle upon Tyne UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Henrique","family":"Lemos","sequence":"additional","affiliation":[{"name":"Newcastle University Translational and Clinical Research Institute Newcastle University  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