The present invention concerns methods for
• in vitro detection of human subjects infected with Mycobacterium tuberculosis but with no clinical symptoms of tuberculosis. It allows the distinction between the latently infected subjects, those who are uninfected and those who suffer from active tuberculosis. The method allows the detection of both recently infected subjects and subjects who were infected several years before performing the test.
• In vitro detection of human subjects presenting pulmonary and extra-pulmonary active tuberculosis
POTENTIAL APPLICATIONS AND KEY ADVANTAGES OF THE TECHNOLOGY
It is estimated that one third of the world population is infected with Mycobacterium tuberculosis and that 5-10 % of them will develop active tuberculosis during their lifetime. The risk to develop active tuberculosis is higher in different groups of patients at risk like HIV-infected subjects, patients with end-stage terminal disease, patients under severe immunosuppressive treatment (for autoimmune diseases, after solid grafts etc…), patients under biotherapies, etc.
It is therefore recommended to detect latent Mycobacterium tuberculosis infection mostly in groups of patients who are most at risk to reactivate the infection and to develop active tuberculosis, in order to treat them prophylactically. This can only be done with a test detecting all the latently infected subjects with a high sensitivity, allowing to differentiate them from active tuberculosis, and if possible determining an index risk factor. Such a test is not available on the market.
It is also recommended to treat very quickly any new case of active tuberculosis and the classical diagnosis by isolation of the bacteria often needs several weeks to be positive and often gives false negative results for extra-pulmonary tuberculosis.
The present invention enables:
• Discrimination between latent and active infection,
• Risk Profiling of patients to develop active tuberculosis.
• Extra-Pulmonary Active Tuberculosis Diagnostic
TECHNOLOGY DEVELOPMENT STAGE
The test validation has been in process for more than 4 years within the Hôpital Erasme:
-96 hours Test on peripheral blood mononuclear cells validated, with ELISA read-out
• “Heparin-Binding-Hemagglutinin-Induced IFN-γ Release as a Diagnostic Tool for Latent Tuberculosis”
Jean-Michel Hougardy, Kinda Schepers, Sammy Place, Annie Drowart, Ve´ronique Lechevin, Virginie Verscheure, Anne-Sophie Debrie, T. Mark Doherty, Jean-Paul Van Vooren, Camille Locht, Françoise Mascart
• “Risk Stratification of Latent Tuberculosis Defined by Combined Interferon Gamma Release Assays”
V Corbière, G Pottier, F Bonkain, K Schepers, V Verscheure, S Lecher, T M Doherty, C Locht, F Mascart. PlosOne 2012
-24 hours Test on peripheral blood mononuclear cells validated, with ELISA read-out
• “24 hours-HBHA-specific interferon-gamma release assay for the detection of latent tuberculosis”
C Wyndham-Thomas, V Corbière, V Dirix, K Smits, F Domont, M Libin, S Vanderseypen, M loyens, C Locht, F Mascart (submitted)
• “Heparin-binding haemagglutinin, a new tool for the detection of latent Mycobacterium tuberculosis infection in hemodialysis patients”
R Dessein, V Corbière, Y tournay, J Nortier, M dratwa, K Gastaldello, A Pozdzik, S lecher, B Grandbastien, C Locht, F Mascart (submitted)
Cohorts currently tested :
• HIV-infected patients
• Screening for latent tuberculosis before starting anti-TNF-a treatment
• Screening for latent tuberculosis before solid graft
• Screening of patients with uveitis that may be secondary to a Mtb infection
- 24 hours Test validated on lymphocytes collected at the site of infection, with flow cytometry read-out
• “Heparin-binding Hemagglutinin-specific IFN-γ Synthesis at the Site of Infection during Active
Tuberculosis in Humans »
S Place, V Verscheure, N de San, J-M Hougardy, K Schepers, V Dirix, A Dediste, O Michel, A Drowart, S D Allard, T M Doherty, S Lecher, C Locht, and F Mascart. AJRCCM 2010
2)HBHA antigen Production and Purification
-Size and purity controlled by SDS-PAGE followed by mass spectrometry analyses (including detailed analyses of the methylated region)
-Control of the specific methylation profile by sandwich ELISA
-Stability : at least 1 year at -20°C and at least 2 weeks at 4°C (i.e. no protein degradation)
-Potential scale up to industrial batch sizes: in progress (Potential partnership withn an American Association interested in producing industrialized quantity of the antigen).
Type of Business Relationship Sought
Licensing, research and development collaborations
Last Updated Sep 2014