IFN-γ-independent immune markers of Mycobacterium tuberculosis exposure
Name
s41591-019-0441-3.pdf
Description
Published version
Size
8.8 MB
Format
Adobe PDF
Checksum (MD5)
f97c176055732452e04bcf0ce6d8f18c
Author(s)
Lu, Lenette L.
Smith, Malisa T.
Yu, Krystle K. Q.
Luedemann, Corinne
Suscovich, Todd J.
Grace, Patricia S.
Cain, Adam
Yu, Wen-Han
McKitrick, Tanya R.
Lauffenburger, Douglas A
Date Issued
May 2019
Journal
Nature Medicine
Publisher
Springer Science and Business Media LLC
Citation
Lu, Lenette L. et al. "IFN-γ-independent immune markers of Mycobacterium tuberculosis exposure." Nature Medicine 25, 6 (May 2019): 977–987 © 2019 The Author(s)
Version
Final published version
Abstract
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.
MIT Department
Massachusetts Institute of Technology. Department of Biological Engineering
Terms of Use
Creative Commons Attribution 4.0 International license
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DOI of Published Version
http://dx.doi.org/10.1038/s41591-019-0441-3
