Heterogeneity of the cytokinome in undifferentiated arthritis progressing to rheumatoid arthritis and its change in the course of therapy. Move toward personalized medicine

Objectives: To conduct a comprehensive analysis of cytokine concentrations in sera and mononuclear cell supernatants in order to examine inter- and intra-individual cytokine variations in undifferentiated arthritis progressing to rheumatoid arthritis and healthy control groups. Methods: Patients with UA (undifferentiated arthritis) developing RA (rheumatoid arthritis) (UA -> RA) (n = 16) and healthy controls (n = 16) were enrolled into the study. UA -> RA patients were followed up for six months since the final RA diagnosis. Cytokines IFN-gamma, IL-10, TNF, IL-17A, IL-6, IL-1 beta, IL-2 in sera and mononuclear cell supernatants in 72 h and 120 h culture variants with- and without anti-CD3 stimulations were assayed using flow cytometric bead array. Results: The cytokine profile of UA -> RA differs from the healthy individual cytokine profile. It is possible to observe specific cytokine pattern characterizing each patient, which alters during course of disease. Specifically, we can distinguish three UA -> RA cohorts: the group of patients susceptible to the therapy, characterized by the drop of cytokine levels between 1st and 3rd visit with visible decrease of cytokines in 2nd visit and then secondary slighter increase in 3rd visit; the group of patients refractory or clinically worsening on the therapy, characterized by the highest cytokine levels at 2nd visit with secondary decrease in 3rd visit; and the group of patients with variable responses to the therapy without any specific common cytokine pattern. The cytokine patterns in supematants of PBMC stimulated anti-CD3 for 72 h and 120 h are very similar. Conclusions: The personal profile including multiplexed cytokine patterns in serum and supernatant may be potentially used for optimization of therapy introduction and monitoring.