Poster Presentation HUPO 2019 - 18th Human Proteome Organization World Congress

Multiple Biomarker Panel to Predict Response to Tocilizumab(anti-IL6R) in Rheumatoid Arthritis Patients Using High-precision Proteomics Approach (#602)

Jinwoo Jung 1 , Byoung-Kyu Cho 1 , Yeong Wook Song 2 , Eugene. C Yi 1
  1. Department of Molecular Medicine and Biopharmaceutical Sciences, Graduate School of Convergence Science and Technology, Seoul National University, Seoul, South Korea
  2. Division of Rheumatology, Department of Internal Medicine, College of Medicine, Seoul National University, Seoul, South Korea

Rheumatoid arthritis (RA) is a common chronic and systemic autoimmune diseases that cause inflammation of the thin layer of tissue lining the joints. Interleukin-6 (IL-6), along with TNF-a and several inflammatory cytokines, acts a vital role in activation of local synovial leukocyte production and induction of chronic inflammation. A humanized anti-IL-6 receptor(IL-6R) monoclonal antibody, Tocilizumab (TCZ), has been demonstrated a significant clinical efficacy for RA patients. However, like other inflammatory cytokine blockers such as TNF-a, Interleukin-1 (IL-1), or CD20 inhibitors, some patients still show a partial respond or resistant to the treatment. This study therefore aimed at identifying protein biomarkers that could predict clinical response against TCZ in RA patients by implementing high-precision proteomics approach. We first identified 54 serum protein biomarker candidates from a large-scale serum proteome profiling of TCZ responder and non-responder groups. Selected protein biomarker candidates combined with known RA biomarkers from the literature data mining were verified by two different targeted quantification methods; multiple reaction monitoring (MRM) and parallel reaction monitoring (PRM) with Triple-quadrupole (QqQ) and Q-Exactive (QE), respectively. Moreover, we validated the results with 47 individual serum samples using MRM and developed as a multi-biomarker panel. The constructed 4-biomarker panel showed 83% discriminate power in average between two different groups with high AUC value of 0.859. The panel also shows 82% sensitivity and 84% specificity of its innate validity. Collectively, our multi-biomarker panel implies that 4 selected proteins were able to serve as diagnostic assessments to predict the TCZ non-responders in RA patients and possible to supplement serum biomarker discovery-validation process in the clinical field based on integrative proteomic approach.