University of Cape Town

Seattle Children's Hospital

Max-Planck-Gesellschaft Zur F&#xf6;rderung Der Wissenschaften E. V.

Stellenbosch University

United Kingdom Research and Innovation

Seattle Children's Hospital Dba Seattle Children's Research Institute

Daniel Edward Zak

Ethan Greene Thompson

Thomas Jens Scriba

Stefan H E Kaufmann

Alan Arnold Aderem

Gerhard Walzl

Adam Garth Penn-Nicholson

Jayne Suzanne Sutherland

Sara Suliman

Willem Albert Hanekom

The invention provides a gene signature for use in determining a likelihood of a latent tuberculosis (TB) infection in a subject transitioning to active TB disease. The gene signature comprises at least SEPT4 and BLK, and optionally also GAS6 and/or CD1C. Expression levels of these genes are detected in a sample from the subject, and the ratios of expression of at least two of the above genes are calculated (e.g. SEPT4:BLK, SEPT4:CD1C, GAS6:BLK and/or GAS6:CD1C). A score is assigned to each ratio, the score being indicative of the likelihood of the latent TB infection transitioning into active TB disease, based on the ratio for the respective gene pair. The subject can be identified as having a latent TB infection that is likely to transition into active TB disease or that is not likely to transition into active TB disease based on the score or on the average of the scores.

Method for predicting progression to active tuberculosis disease

This invention relates to a prognostic method for determining the risk of an asymptomatic human subject with latent tuberculosis (TB) infection or apparent latent TB infection and/or after suspected exposure to TB progressing to active tuberculosis disease comprising the steps of quantifying and computationally analysing relative abundances of a collection of pairs of gene products ('TB biomarkers') derived from a sample obtained from the subject. The invention further relates to a collection of TB biomarkers that generates a transcriptomic signature of risk for prediction of the likelihood of an asymptomatic human subject with latent TB infection and/or after suspected exposure to TB progressing to active tuberculosis disease. Furthermore, a kit comprising gene-specific primers or oligonucleotide probes for the detection of pairs of TB biomarkers that generates a prognostic signature of risk for use with the method of the invention is described. In addition, the invention relates to a method of preventive treatment or prophylaxis for TB infection comprising the use of the prognostic method and/or the kit of the invention to select an appropriate or experimental treatment regime or intervention for the human subject and/or to monitor the response of the human subject to the TB prophylaxis.

Biomarkers for prospective determination of risk for development of active tuberculosis

Growing community of inventors

Seattle, WA, United States of America

Daniel Edward Zak