The human antibody response to the surface of Mycobacterium tuberculosis.

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.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).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).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

Univariate correlation between clinical variables and total antibody titers to the live <i>M. tuberculosis</i> surface or to whole cell lysate in patients with active TB disease (n = 40).

<p>*P-value calculated using one-way ANOVA for categorical variables with >2 categories, students t-test for categorical variables with 2 categories and F-statistic for continuous variables. Welch’s correction was applied to the student’s t-test when variances were not equal between groups. All p-values are unadjusted for multiple comparisons.</p

Antibody (Ab) responses to <i>M. tuberculosis</i> to lipoarabinomannan, cell wall, and secreted protein fractions.

<p>Plasma from PPD-negative volunteers (Uninfected), patients with latent TB infection (Latent), or patients with active TB disease (Active) were assayed by ELISA against the surface of live <i>M. tuberculosis</i> H37Rv or H37Rv whole cell lysate. (<b>A–C</b>) Log₁₀ total Ig titers. (<b>D–F</b>) Relative IgG avidity. (<b>G–I</b>) Log₁₀ ratio of IgG to IgM titers. Two-sided p-values by student’s t-test or Mann-Whitney test: (*) p≤0.05, (**) p≤0.01, (***) p≤0.001.</p

Reactivity of human plasma to surface of environmental mycobacteria.

<p>Plasma from PPD-negative volunteers (Uninfected), patients with latent TB infection (Latent), or patients with active TB disease (Active) were assayed by ELISA against the surface of live <i>M. intracellulare</i> (<b>A,D</b>) <i>M. avium </i><b>(B,E</b>), and <i>M. fortuitum </i><b>(C,F</b>). Log₁₀ total Ig titers and relative IgG avidity are displayed. Two-sided p-values by student’s t-test or Mann-Whitney test: (*) p≤0.05, (**) p≤0.01, (***) p≤0.001.</p

Demographic and clinical data.

<p>*Percentages may not add to 100% due to rounding.</p

Univariate correlation between clinical variables and relative IgG avidity of antibodies to the live <i>M. tuberculosis</i> surface or to whole cell lysate in patients with active TB disease (n = 40).

<p>*P-value calculated using one-way ANOVA for categorical variables with >2 categories, students t-test for categorical variables with 2 categories and F-statistic for continuous variables. Welch’s correction was applied to the student’s t-test when variances were not equal between groups. All p-values are unadjusted for multiple comparisons.</p