JAK signaling was involved in the pathogenesis of Polymyalgia Rheumatica

Objectives Polymyalgia Rheumatica (PMR) is a common inflammatory disease in elderly persons whose pathogenesis is unclear. We aimed to explore the pathogenetic features of PMR and find a new therapeutic strategy. Methods We included 11 patients with PMR and 20 age-matched and sex-matched healthy controls (HC) in this study. The disease features were described. The gene expression profiles were analyzed in peripheral blood mononuclear cells (PBMCs) by RNA sequencing and were confirmed by RT-PCR. We also tested gene expression profiles in five patients with PMR after tofacitinib therapy. Results Patients with PMR experienced pain with high disease activity scores. The gene expression of PBMCs in patients with PMR differed from that in HC by RNA sequencing. GO and KEGG analysis demonstrated that inflammatory response and cytokine-cytokine receptor interaction were the most remarkable pathways. There were markedly expanded IL6R, IL1B, IL1R1, JAK2, TLR2, TLR4, TLR8, CCR1, CR1, S100A8, S100A12, and IL17RA expressions. Those genes may trigger the JAK signaling. Furthermore, tofacitinib, a pan JAK inhibitor, effectively treated five patients with PMR, leading to clinical remission and a significant decrease in inflammatory genes. Conclusions Many inflammatory genes associated with JAK signaling were increased in patients with PMR, suggesting an important role of JAK signaling in PMR disease development. JAK inhibitors may effectively treat PMR. Key messages Patients with PMR had significant inflammatory genes expression. JAK signaling may be highly activated. Tofacitinib may treat PMR with clinical remission and a significant decrease in inflammatory genes.