Opti-4TB: A protocol for a prospective cohort study evaluating the performance of new biomarkers for active tuberculosis outcome prediction

IntroductionTuberculosis (TB) treatment requires the combination of multiple anti-TB drugs during 6 months or more depending on strain drug susceptibility profile. Optimizing the monitoring of anti-TB therapy efficacy is required to provide adequate care and prevent drug resistance emergence. Moreover, accurate monitoring tools are needed for the development of strategies aiming at reducing treatment duration. Opti-4TB is a "proof of concept " study aiming at developing a blood-based monitoring of TB outcome by deciphering host immune signatures associated with latency or disease activity through the combination of "omic " methods. The primary objective is to assess the performances of new biomarkers for TB outcome prediction and to determine specific profiles associated with the outcome of treated TB patients.Methods and analysisOpti-4TB is a prospective, single center study including adult patients hospitalized for pulmonary TB. A workflow will be set up to study the immune status of 40 TB patients and 20 controls with latent TB infection. Blood samples will be collected at four timepoints: before treatment initiation (V1), at day 15 (V2), at 2 months (V3) and at 6 months (V4). Mtb-specific immune responses will be assessed at each timepoint with three different assays: (1) A whole blood transcriptomic signature assessing the "RISK-6 " score; (2) A proteomic signature based on 27 cytokines and chemokines measured in plasma; (3) An immunophenotypic monitoring of circulating T-cell subpopulations using spectral flow cytometry. This in depth characterization of Mtb-specific immune response throughout the treatment, correlated with clinical outcomes, will lay the basis for the elaboration of the most basic and universal stage-specific immune signatures associated with latency, active disease and cure.Ethics and disseminationEthical approval has been obtained from the institutional review board (n & DEG;69HCL18_0757). Results will be communicated at scientific meetings and submitted for publication in peer-reviewed journals.