%0 Journal Article
%T IFN-¦Ă-independent immune markers of Mycobacterium tuberculosis exposure
%J -
%D 2019
%R https://doi.org/10.1038/s41591-019-0441-3
%X 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-¦Ă (IFN-¦Ă) 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-¦Ă 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-¦Ă 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
%U https://www.nature.com/articles/s41591-019-0441-3