Impaired Akt Phosphorylation in Monocytes of Patients with Rheumatoid Arthritis

It has been proposed that the Akt kinase pathway provides a regulatory mechanism to limit the inflammatory response. We examined the activation of Akt upon LPS challenge in monocytes of patients with rheumatoid arthritis (RA), and correlated it with disease activity. Twelve subjects with recent-onset, DMARD-naive RA, thirteen patients with chronic, DMARD therapy -nonresponding RA and 27 healthy volunteers provided whole blood samples for phosphospecific flow cytometric measurement of unstimulated and LPS-stimulated Akt phosphorylation at serine 473 in monocytes, determined in relative fluorescence units (RFU). Activation capability, i.e. responsiveness of monocytes, was determined as the difference between stimulated and unstimulated samples, and compared between groups using Mann-Whitney test. CRP and ESR, swollen and tender joint counts, patients’ global assessment of disease activity, DAS28 score, and plasma IL-6 determined by ELISA were correlated with Akt activation using Spearman method. Median (interquartile range) Akt activation capability was significantly lower in DMARD-naive (379 RFU [285, 432],], p=0.016) and even lower in DMARD-nonresponding RA (258 RFU [213, 338], p