Evaluation of Mycobacterium tuberculosis-specific IFN-γ, TNF-α, CXCL10, IL2, CCL2, CCL7 and CCL4 levels for active tuberculosis diagnosis

Our study evaluates seven previously reported biomarkers for active tuberculosis (ATB) diagnosis. We compared Mycobacterium tuberculosis -specific IFN-γ, TNF-α, CXCL10, IL2, CCL2, CCL7 and CCL4 levels in patients with ATB and non-tuberculosis respiratory diseases. Our ATB group included equal numbers of patients with positive and negative QuantiFERON-TB Gold In-Tube (QFT-GIT) results, to assess whether any biomarker offered superior diagnostic accuracy to IFN-γ. No biomarker achieved higher sensitivity than QFT-GIT for ATB diagnosis without significant loss of specificity. Our study design provides an efficient strategy for rapidly gating future biomarkers by using clinically relevant and representative patient groups in whom current QFT-GIT tests fail. ### Competing Interest Statement AL reports issued patents underpinning IGRA and next-generation IGRA some of which were assigned by the University of Oxford to Oxford Immunotec plc resulting in royalty entitlements for the University of Oxford and AL. AL is also inventor of issued and pending unlicensed patents underpinning flow-cytometric diagnosis of TB. No other authors report a conflict of interest. ### Funding Statement This work was supported by the National Institute for Health Research Efficacy, Mechanisms and Evaluation Programme, Grant #12/65/27 (Validation of New Technologies for Diagnostic Evaluation of Tuberculosis (VANTDET)). AL is a United Kingdom National Institute for Health Research (NIHR) Senior Investigators Emeritus. ### Author Declarations I confirm all relevant ethical guidelines have been followed, and any necessary IRB and/or ethics committee approvals have been obtained. Yes The details of the IRB/oversight body that provided approval or exemption for the research described are given below: Participants provided written, informed consent. The study was approved by Camden and Islington National Research Ethics Committee (reference 11/H0722/8/). I confirm that all necessary patient/participant consent has been obtained and the appropriate institutional forms have been archived, and that any patient/participant/sample identifiers included were not known to anyone (e.g., hospital staff, patients or participants themselves) outside the research group so cannot be used to identify individuals. Yes I understand that all clinical trials and any other prospective interventional studies must be registered with an ICMJE-approved registry, such as ClinicalTrials.gov. I confirm that any such study reported in the manuscript has been registered and the trial registration ID is provided (note: if posting a prospective study registered retrospectively, please provide a statement in the trial ID field explaining why the study was not registered in advance). Yes I have followed all appropriate research reporting guidelines and uploaded the relevant EQUATOR Network research reporting checklist(s) and other pertinent material as supplementary files, if applicable. Yes All data produced in the present study are available upon reasonable request to the authors