Immunological Signatures Identifying Different Stages of Latent Mycobacterium tuberculosis Infection and Discriminating Latent from Active Tuberculosis in Humans
|Kaatje Smits1, Véronique Corbière1, Violette Dirix1, Leila Mekkaoui1, Chloé Wyndham-Thomas1, Myriam Libin1, Alexandra Dreesman1, Marc Loyens2-5, Marie-Christine Payen6, Mahavir Singh7, Camille Locht2-5 and Françoise Mascart1,8*|
|1Laboratory of Vaccinology and Mucosal Immunity, Université Libre de Bruxelles (U.L.B.), Brussels, Belgium|
|2INSERM U 1019, Lille, France|
|3CNRS, UMR8204, Lille, France|
|4Université de Lille, Lille, France|
|5Institut Pasteur de Lille, Centre d’Infection et d’Immunité de Lille, Lille, France|
|6Department of Infectious Diseases, CHU Saint-Pierre, Université Libre de Bruxelles (U.L.B.), Brussels, Belgium|
|7Lionex, Braunschweig, Germany|
|8Immunobiology Clinic, Hôpital Erasme, Université Libre de Bruxelles (U.L.B.), Brussels, Belgium|
|Corresponding Author :||Françoise Mascart
Immunobiology Clinic, Hôpital Erasme
Université Libre de Bruxelles (U.L.B.)
E-mail: [email protected]
|Received: April 25, 2015 Accepted: July 10, 2015 Published: July 15, 2015|
|Citation: Smits K, Corbière V, Dirix V, Mekkaoui L, Wyndham-Thomas C, et al. (2015) Immunological Signatures Identifying Different Stages of Latent Mycobacterium tuberculosis Infection and Discriminating Latent from Active Tuberculosis in Humans. J Clin Cell Immunol 6:341. doi:10.4172/2155-9899.1000341|
|Copyright: © 2015 Smits K, et al. This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.|
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Objectives: One third of the world population is considered latently infected with Mycobacterium tuberculosis (LTBI) and sterilizing this reservoir of bacteria that may reactivate is required for tuberculosis (TB) elimination. The group of individuals with LTBI is heterogeneous with some of them being more at risk to develop TB disease than others. Improved diagnosis of subjects with LTBI is needed, allowing to differentiate subjects with LTBI from those with active TB, and to select among LTBI subjects those who are more at risk to develop active TB. We have characterized at the cellular level both the quantitative and qualitative T cell responses to different mycobacterial antigens in selected populations of infected subjects in order to identify new biomarkers that could help to identify M. tuberculosis-infected subjects and to stratify them in risk groups for reactivation of the infection.
Methods: lymphoblast frequencies and cytokine production (IFN-γ, TNF-α, IL-2) among CD4+ and CD8+ T cells were analyzed by flow cytometry after in vitro stimulation with the latency antigen heparin-binding haemagglutinin (HBHA) or early-secreted antigen Target-6 (ESAT-6) of peripheral blood mononuclear cells from clinically well characterized M. tuberculosis-infected humans (28 LTBI, 22 TB disease,12 controls). The LTBI group defined according to the Center for Disease Control guidelines was subdivided into QuantiFERON-TB Gold in-Tube (QFT) positive and negative subgroups.
Results: similar to TB patients, QFT+ LTBI subjects had higher proportions of HBHA-induced TNF-αsingle+ CD4+ lymphocytes than QFT- LTBI subjects (p<0.05). Compared to LTBI subjects, TB patients had higher frequencies of ESAT-6-induced CD8+ lymphoblasts (p<0.001), higher proportions of ESAT-6-induced IFN-γ+TNF-α+ CD4+ T lymphocytes (p<0.05), and lower proportions of HBHA-induced IFN-γ+TNF-α+IL-2+ (p<0.05) CD4+ T lymphocytes.
Conclusions: these data provide new biomarkers to discriminate active TB from LTBI, and more interestingly, help to identify LTBI subjects with increased likelihood to develop TB disease.