• Transl Res · Nov 2024

    A multi-biomarker panel for predicting Tocilizumab response in Rheumatoid arthritis patients.

    • Ara Cho, Jinsung Ahn, Andrew Kim, Yun Jong Lee, Yeong Wook Song, Yoshiya Tanaka, and Eugene C Yi.
    • Department of Molecular Medicine and Biopharmaceutical Sciences, Seoul National University, Graduate School of Convergence Science and Technology, South Korea. Electronic address: ara.cho@snu.ac.kr.
    • Transl Res. 2024 Nov 1; 273: 233123-31.

    AbstractRheumatoid arthritis (RA) is a chronic systemic autoimmune disease characterized by inflammation in the synovial lining of the joints. Key inflammatory cytokines such as interleukin-6 (IL-6), TNF-α, and others play a critical role in the activation of local synovial leukocytes and the induction of chronic inflammation. Tocilizumab (TCZ), a humanized anti-IL-6 receptor monoclonal antibody, has demonstrated significant clinical efficacy in treating RA patients. However, similar to other inflammatory cytokine blockers, such as TNF-alpha inhibitors, Interleukin-1 inhibitors, or CD20 inhibitors, some patients do not respond to treatment. To address this challenge, our study employed a high-precision proteomics approach to identify protein biomarkers capable of predicting clinical responses to Tocilizumab in RA patients. Through the use of data-independent acquisition (DIA) mass spectrometry, we analyzed serum samples from both TCZ responders and non-responders to discover potential biomarker candidates. These candidates were subsequently validated using individual serum samples from two independent cohorts: a training set (N = 70) and a test set (N = 18), allowing for the development of a robust multi-biomarker panel. The constructed multi-biomarker panel demonstrated an average discriminative power of 86 % between response and non-response groups, with a high area under the curve (AUC) value of 0.84. Additionally, the panel exhibited 100 % sensitivity and 60 % specificity. Collectively, our multi-biomarker panel holds promise as a diagnostic tool to predict non-responders to TCZ treatment in RA patients.Copyright © 2024 The Authors. Published by Elsevier Inc. All rights reserved.

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