TY - JOUR
T1 - Immunogenicity of mycobacterial vesicles in humans
T2 - Identification of a new tuberculosis antibody biomarker
AU - Ziegenbalg, Anke
AU - Prados-Rosales, Rafael
AU - Jenny-Avital, Elisabeth R.
AU - Kim, Ryung S.
AU - Casadevall, Arturo
AU - Achkar, Jacqueline M.
N1 - Funding Information:
This work was supported by funds from the National Institute of Health (NIH)/National Institute of Allergy and Infectious Diseases (NIAID; AI-067665 to J.M.A. and AI-033774 , AI-052733 , AI-033142 to A.C.) and the National Heart, Lung, and Blood Institute (NHLBI; HL-059842 to A.C.), the Center for AIDS Research (CFAR) at the Albert Einstein College of Medicine ( AI-51519 ; J.M.A.), the Aeras TB vaccine foundation (R. P.-R.) and the Gates Foundation (J.M.A. and A.C.).
PY - 2013/7
Y1 - 2013/7
N2 - Biomarkers for active tuberculosis (TB) are urgently needed. Mycobacteria produce membrane vesicles (MVs) that contain concentrated immune-modulatory factors that are released into the host. We evaluated the human immune responses to BCG and Mycobacterium tuberculosis MVs to characterize the antibody responses and identify potentially novel TB biomarkers. Serological responses to MVs were evaluated by ELISAs and immunoblots with sera from 16 sputum smear-positive, 12 smear-negative HIV uninfected pulmonary TB patients and 16 BCG vaccinated Tuberculin skin-test positive controls with and without latent tuberculosis infection. MVs from both BCG and M. tuberculosis induced similar responses and were strongly immunogenic in TB patients but not in controls. Several MV-associated antigens appear to induce robust antibody responses, in particular the arabinomanan portion of the cell wall glycolipid lipoarabinomannan. Three proteins at ∼36, 25, and 23 kDa were simultaneously recognized by sera from 16/16 smear-positive, 9/12 smear-negative TB patients and 0/16 controls. These results provide promise and encouragement that antibody responses to proteins enriched in MVs of pathogenic mycobacteria may constitute a novel TB biomarker signature that could have diagnostic information.
AB - Biomarkers for active tuberculosis (TB) are urgently needed. Mycobacteria produce membrane vesicles (MVs) that contain concentrated immune-modulatory factors that are released into the host. We evaluated the human immune responses to BCG and Mycobacterium tuberculosis MVs to characterize the antibody responses and identify potentially novel TB biomarkers. Serological responses to MVs were evaluated by ELISAs and immunoblots with sera from 16 sputum smear-positive, 12 smear-negative HIV uninfected pulmonary TB patients and 16 BCG vaccinated Tuberculin skin-test positive controls with and without latent tuberculosis infection. MVs from both BCG and M. tuberculosis induced similar responses and were strongly immunogenic in TB patients but not in controls. Several MV-associated antigens appear to induce robust antibody responses, in particular the arabinomanan portion of the cell wall glycolipid lipoarabinomannan. Three proteins at ∼36, 25, and 23 kDa were simultaneously recognized by sera from 16/16 smear-positive, 9/12 smear-negative TB patients and 0/16 controls. These results provide promise and encouragement that antibody responses to proteins enriched in MVs of pathogenic mycobacteria may constitute a novel TB biomarker signature that could have diagnostic information.
KW - Diagnostics
KW - Human studies
KW - Immunoglobulins
KW - Infection
KW - Serology
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U2 - 10.1016/j.tube.2013.03.001
DO - 10.1016/j.tube.2013.03.001
M3 - Article
C2 - 23562367
AN - SCOPUS:84878903698
SN - 1472-9792
VL - 93
SP - 448
EP - 455
JO - Bulletin of the International Union Against Tuberculosis and Lung Disease
JF - Bulletin of the International Union Against Tuberculosis and Lung Disease
IS - 4
ER -
