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

Rheumatoid 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.

Serum levels of leptin and adiponectin in patients with autoimmune Hashimoto's thyroiditis.

INTRODUCTION: Adipose tissue is immunologically and hormonally active, and these effects are mediated largely by adipocytokines. Thyroid hormones regulate metabolism and organ function, and Hashimoto's thyroiditis (HT) is the most common autoimmune disease affecting thyroid function. AIM: To evaluate the levels of the adipocytokines leptin and adiponectin in patients with autoimmune HT, and to perform a comparative intragroup analysis in patients with different stages of gland functional activity, and in a control group. MATERIALS AND METHODS: Ninety-five patients with HT and 21 healthy controls were enrolled in the study. Venous blood was taken without anticoagulants after at least 12 hours of fasting, and serum samples were frozen at -70°C until analysis. Serum levels of leptin and adiponectin were determined by an enzyme-linked immunosorbent assay (ELISA). RESULTS: Serum levels of leptin in HT patients were higher than those in the control group (4.5±5.2 ng/mL vs. 1.9±1.3 ng/mL). The hypothyroid patient's group showed significantly higher levels of leptin than those of the healthy controls (5.1±5.2 ng/mL vs. 1.9±1.3 ng/mL), (p=0.031). Leptin levels correlated positively with body mass index (r=0.533, p.