JAK inhibitors improve ATP production and mitochondrial function in rheumatoid arthritis: a pilot study

Springer Science and Business Media LLC - Tập 44 Số 1 - Trang 57-65
Valentina N Mihaylova1,2, Maria Kazakova1,2, Z Batalov3,4, Rositsa Karalilova3,4, Anastas Batalov3,4, Мaria Semerdjieva1,2
1Department of Medical Biology, Medical University-Plovdiv, Plovdiv, Bulgaria
2Research Institute at Medical University-Plovdiv, Plovdiv, Bulgaria
3Clinic of Rheumatology, University Hospital “Kaspela”, Plovdiv, Bulgaria
4Department of Propedeutics of Internal Diseases, Medical University-Plovdiv, Plovdiv, Bulgaria

Tóm tắt

AbstractRheumatoid arthritis (RA) is a chronic, systemic autoimmune disease associated by inflammation of the synovial tissue and autoantibody production. Oxidative stress and free radicals are known to be indirectly implicated in joint damage and cartilage destruction in RA. Several studies describe the presence of mitochondrial dysfunction in RA, but few of them follow the dynamics in energy parameters after therapy. The aim of our investigation is to evaluate the direct effect of JAK inhibitors on cellular metabolism (and under induced oxidative stress) in RA patients. Ten newly diagnosed RA patients were included in the study. Peripheral blood mononuclear cells (PBMCs) and plasma were isolated before and 6 months after therapy with JAK inhibitors. A real-time metabolic analysis was performed to assess mitochondrial function and cell metabolism in PBMCs. Sonographic examination, DAS28 and conventional clinical laboratory parameters were determined also prior and post therapy. A significant decrease in proton leak after therapy with JAK inhibitors was found. The increased production of ATP indicates improvement of cellular bioenergetics status. These findings could be related to the catalytic action of JAK inhibitors on oxidative phosphorylation which corresponds to the amelioration of clinical and ultra-sonographic parameters after treatment. Our study is the first to establish the dynamics of mitochondrial parameters in PBMCs from RA patients before and after in vivo therapy with JAK inhibitors.

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Springer Science and Business Media LLC

Tập 44 Số 1

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