The Human Antibody Response to the Surface of Mycobacterium tuberculosis

Abstract

BackgroundVaccine-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.MethodsPlasma 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).ResultsWhen 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/SignificanceHumans 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.

Diagnostic value of antibody responses to multiple antigens from Mycobacterium tuberculosis in active and latent tuberculosis

“…This finding is supported by several other studies that found higher levels of anti-LAM IgG in HIV-negative patients with TB, compared to controls with a positive TST result [22,23]. The study of Perley et al showed that anti-LAM titers were similar among healthy, latent and active TB subjects, however LTBI subjects had avidity intermediate between uninfected controls and active TB patient [24]. In the same study, the MAC positivity in studied groups was not clearly described, therefore the possible antibody cross reaction between species could not be excluded.…”

Effects of Serial Skin Testing with Purified Protein Derivative on the Level and Quality of Antibodies to Complex and Defined Antigens in Mycobacterium bovis-Infected Cattle

“…Early after antimycobacterial therapy for M. tuberculosis infections in humans, there is a decrease in antibody avidity accompanied by an initial increase in serum antibody levels, likely due to the bactericidal activity of antituberculous drugs leading to low-affinity antibodies to released antigens (38). Also, humans with active tuberculosis produce low-avidity antibodies with low IgG/IgM ratios for surface antigens of M. tuberculosis but higher-avidity antibodies with higher IgG/IgM ratios for cellular fractions of antigens, potentially indicating immune evasion strategies of this highly successful pathogen, given the association with protection for highly avid antibodies to surface components of other bacteria (39). With experimental M. bovis infection, the disease is generally considered slowly progressive (40,41), thus most closely resembling the active form of the disease in humans.…”

Latently and uninfected healthcare workers exposed to TB make protective antibodies against Mycobacterium tuberculosis

“…Although it was known that both active TB patients and healthy subjects make detectable antibody responses to Mtb (19)(20)(21), it was not known whether any of these antibodies afford direct protection against infection. We decided to test total antibody from our subjects in a mouse protection assay (Fig.…”