Determination of Heterogeneous Proteomic and Metabolomic Response in anti-TNF and anti-IL-6 Treatment of Patients with Rheumatoid Arthritis

Abstract

Reduction in tumor necrosis factor (αTNF) and interleukin-6 (IL-6) activities is a widely utilized strategy for the treatment of rheumatoid arthritis (RA) with a high success rate. Despite both schemes targeting the deprivation of inflammatory reactions caused by the excessive activity of cytokines, their mechanisms of action and the final output are still unequal. This was a comparative longitudinal study that lasted for 24 weeks and aimed to find the answer to why the two schemes of therapy can pass out of proportion in attitude of their efficiency. What are the differences in metabolic and proteomic responses among patients who were being treated by either the anti-TNF or anti-IL-6 strategy? We found increased levels of immunoglobulins A and G (more than 2-fold in anti-IL-6 and more than 4-5-fold in anti-TNF groups) at the final stage (24 weeks) of monitoring but the most profound increase was determined for µ-chains of immunoglobulins in both groups of study. Metabolomic changes displayed main alterations with regard to arginine metabolism and collagen maintenance, where arginine increased 8.86-fold (p < 0.001) in anti-TNF and 5.71-fold (p < 0.05) in anti-IL-6 groups but patients treated by the anti-TNF scheme suffered a higher depletion of arginine before the start of therapy. Some indicators of matrix and bone tissue degradation also increased 4-hydroxyproline (4-HP) more than 6-fold (p < 0.001) in anti-TNF and more than 2-fold (p < 0.05) in the anti-IL-6 group, but the growth dynamics in the anti-IL6 group was delayed (gradually raised at week 24) compared to the anti-TNF group (raised at week 12) following a smooth reduction. The ELISA analysis of IL-6 and TNFα concentration in the study population supported proteomic and metabolomic data. A positive correlation between ΔCDAI and ΔDAS28 indicators and ESR and CRP was established for the majority of patients after 24 weeks of treatment where ESR and CRP reduced by 20% and 40% finally, respectively. A regression model using the Forest Plot was estimated to elucidate the impact of the most significant clinical, biochemical, and anthropometric indicators for the evaluation of differences between considered anti-TNF and anti-IL-6 schemes of therapy.