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|a Lu, Lenette L.
|e author
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|a Massachusetts Institute of Technology. Department of Biological Engineering
|e contributor
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|a Smith, Malisa T.
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|a Yu, Krystle K. Q.
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|a Luedemann, Corinne
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|a Suscovich, Todd J.
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|a Grace, Patricia S.
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|a Cain, Adam
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|a Yu, Wen-Han
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|a McKitrick, Tanya R.
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|a Lauffenburger, Douglas A
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|a Cummings, Richard D.
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|a Mayanja-Kizza, Harriet
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|a Hawn, Thomas R.
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|a Boom, W. Henry
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|a Stein, Catherine M.
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|a Fortune, Sarah M.
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|a Seshadri, Chetan
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|a Alter, Galit
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|a IFN-γ-independent immune markers of Mycobacterium tuberculosis exposure
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|b Springer Science and Business Media LLC,
|c 2020-06-25T14:49:00Z.
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|z Get fulltext
|u https://hdl.handle.net/1721.1/125979
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|a Exposure to Mycobacterium tuberculosis (Mtb) results in heterogeneous clinical outcomes including primary progressive tuberculosis and latent Mtb infection (LTBI). Mtb infection is identified using the tuberculin skin test and interferon-γ (IFN-γ) release assay IGRA, and a positive result may prompt chemoprophylaxis to prevent progression to tuberculosis. In the present study, we report on a cohort of Ugandan individuals who were household contacts of patients with TB. These individuals were highly exposed to Mtb but tested negative disease by IFN-γ release assay and tuberculin skin test, 'resisting' development of classic LTBI. We show that 'resisters' possess IgM, class-switched IgG antibody responses and non-IFN-γ T cell responses to the Mtb-specific proteins ESAT6 and CFP10, immunologic evidence of exposure to Mtb. Compared to subjects with classic LTBI, 'resisters' display enhanced antibody avidity and distinct Mtb-specific IgG Fc profiles. These data reveal a distinctive adaptive immune profile among Mtb-exposed subjects, supporting an expanded definition of the host response to Mtb exposure, with implications for public health and the design of clinical trials.
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|a Bill and Melinda Gates Foundation (Grant OPP1109001)
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|a Bill and Melinda Gates Foundation (Grant OPP1151840)
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|a Bill and Melinda Gates Foundation (Grant OPP1156795)
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|a en
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|a Article
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|t Nature Medicine
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