The human antibody response to the surface of Mycobacterium tuberculosis.

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Perley, Casey C

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Frahm, Marc

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Click, Eva M

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Dobos, Karen M

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Ferrari, Guido

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Stout, Jason E

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Frothingham, Richard

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Pai, Madhukar

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United States

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2017-04-01T13:19:36Z

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2017-04-01T13:19:36Z

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2014

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BACKGROUND: Vaccine-induced human antibodies to surface components of Haemophilus influenzae and Streptococcus pneumonia are correlated with protection. Monoclonal antibodies to surface components of Mycobacterium tuberculosis are also protective in animal models. We have characterized human antibodies that bind to the surface of live M. tuberculosis. METHODS: Plasma from humans with latent tuberculosis (TB) infection (n = 23), active TB disease (n = 40), and uninfected controls (n = 9) were assayed by ELISA for reactivity to the live M. tuberculosis surface and to inactivated M. tuberculosis fractions (whole cell lysate, lipoarabinomannan, cell wall, and secreted proteins). RESULTS: When compared to uninfected controls, patients with active TB disease had higher antibody titers to the surface of live M. tuberculosis (Δ = 0.72 log10), whole cell lysate (Δ = 0.82 log10), and secreted proteins (Δ = 0.62 log10), though there was substantial overlap between the two groups. Individuals with active disease had higher relative IgG avidity (Δ = 1.4 to 2.6) to all inactivated fractions. Surprisingly, the relative IgG avidity to the live M. tuberculosis surface was lower in the active disease group than in uninfected controls (Δ =  -1.53, p = 0.004). Patients with active disease had higher IgG than IgM titers for all inactivated fractions (ratios, 2.8 to 10.1), but equal IgG and IgM titers to the live M. tuberculosis surface (ratio, 1.1). Higher antibody titers to the M. tuberculosis surface were observed in active disease patients who were BCG-vaccinated (Δ = 0.55 log10, p = 0.008), foreign-born (Δ = 0.61 log10, p = 0.004), or HIV-seronegative (Δ = 0.60 log10, p = 0.04). Higher relative IgG avidity scores to the M. tuberculosis surface were also observed in active disease patients who were BCG-vaccinated (Δ = 1.12, p < 0.001) and foreign-born (Δ = 0.87, p = 0.01). CONCLUSIONS/SIGNIFICANCE: Humans with active TB disease produce antibodies to the surface of M. tuberculosis with low avidity and with a low IgG/IgM ratio. Highly-avid IgG antibodies to the M. tuberculosis surface may be an appropriate target for future TB vaccines.

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https://www.ncbi.nlm.nih.gov/pubmed/24918450

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PONE-D-14-16147

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1932-6203

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https://hdl.handle.net/10161/13898

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eng

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Public Library of Science (PLoS)

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PLoS One

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10.1371/journal.pone.0098938

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Adult

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Antibodies, Bacterial

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Antibody Affinity

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Antibody Formation

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Female

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Humans

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Immunoglobulin G

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Immunoglobulin M

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Latent Tuberculosis

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Male

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Middle Aged

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Mycobacterium tuberculosis

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Tuberculosis

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Young Adult

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The human antibody response to the surface of Mycobacterium tuberculosis.

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Journal article

duke.contributor.orcid

Ferrari, Guido|0000-0001-7747-3349

duke.contributor.orcid

Stout, Jason E|0000-0002-6698-8176

pubs.author-url

https://www.ncbi.nlm.nih.gov/pubmed/24918450

pubs.begin-page

e98938

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2

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Basic Science Departments

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Clinical Science Departments

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Duke

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Duke Human Vaccine Institute

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Global Health Institute

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Institutes and Centers

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Institutes and Provost's Academic Units

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Medicine

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Medicine, Duke Human Vaccine Institute

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Medicine, Infectious Diseases

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Molecular Genetics and Microbiology

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School of Medicine

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Surgery

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Surgery, Surgical Sciences

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University Institutes and Centers

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Published online

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9

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