Immunoglobulin G subclass responses to mycobacterial lipoarabinomannan in HIV-infected and non-infected patients with tuberculosis

Costa, Cristina; Khanolkar-Young, S.; Elliott, Alison M.; Wasunna, K.

doi:10.1111/j.1365-2249.1993.tb03348.x

Cited by 36 publications

(20 citation statements)

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“…Pre-coating of BCG with anti-HBHA mAbs prior to intranasal inoculation did not influence bacterial CFU in lungs, but led to a marked reduction in spleen colonization [101]. This finding supports previously described studies suggesting that antibodies directed against LAM prevented dissemination of infection and that anti-HBHA IgM is able to prevent epithelial cell invasion [92], [102]. However Parra et al.…”

Section: Introductionsupporting

confidence: 86%

Antibodies and tuberculosis

et al. 2016

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SummaryTuberculosis (TB) remains a major public health problem internationally, causing 9.6 million new cases and 1.5 million deaths worldwide in 2014. The Bacillus Calmette-Guérin vaccine is the only licensed vaccine against TB, but its protective effect does not extend to controlling the development of infectious pulmonary disease in adults. The development of a more effective vaccine against TB is therefore a pressing need for global health. Although it is established that cell-mediated immunity is necessary for the control of latent infection, the presupposition that such immunity is sufficient for vaccine-induced protection has recently been challenged. A greater understanding of protective immunity against TB is required to guide future vaccine strategies against TB.In contrast to cell-mediated immunity, the human antibody response against M.tb is conventionally thought to exert little immune control over the course of infection. Humoral responses are prominent during active TB disease, and have even been postulated to contribute to immunopathology. However, there is evidence to suggest that specific antibodies may limit the dissemination of M.tb, and potentially also play a role in prevention of infection via mucosal immunity. Further, antibodies are now understood to confer protection against a range of intracellular pathogens by modulating immunity via Fc-receptor mediated phagocytosis. In this review, we will explore the evidence that antibody-mediated immunity could be reconsidered in the search for new vaccine strategies against TB.

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Section: Introductionsupporting

confidence: 86%

Antibodies and tuberculosis

et al. 2016

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“…Other studies have shown that HIV infection induces dysregulation in antibody responses to LAM, altering IgG subtype profiles, and decreasing the levels of IgG2 anti- M. tuberculosis antibodies as compared to HIV negative controls [31]. In both aging and HIV-infection, T-cells are also affected.…”

Section: Discussionmentioning

confidence: 99%

The Human Antibody Response to the Surface of Mycobacterium tuberculosis

et al. 2014

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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.

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“…Direct entry from the bloodstream into the urine of Mycobacterium tuberculosis (MTB) seems unlikely, due to its size compared to the size of the filtration slits of an intact glomerular basement membrane (GBM) ( Fig 2 , Mechanism 2)[ 26 ]. LAM is immunogenic and anti-LAM antibodies were detected in both urinary LAM-positive and negative HIV-TB co-infected patients[ 27 , 28 ]. LAM caught in immune-complexes would also be too large the pass an intact GBM ( Fig 2 , Mechanism 3).…”

Section: Discussionmentioning

confidence: 99%

Is Urinary Lipoarabinomannan the Result of Renal Tuberculosis? Assessment of the Renal Histology in an Autopsy Cohort of Ugandan HIV-Infected Adults

et al. 2015

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ObjectiveThe detection of urinary lipoarabinomannan (LAM), a mycobacterial cell wall component, is used to diagnose tuberculosis (TB). How LAM enters the urine is not known. To investigate if urinary LAM-positivity is the result of renal TB infection we correlated the outcomes of urinary LAM-antigen testing to renal histology in an autopsy cohort of hospitalized, Ugandan, HIV-infected adults.MethodsWe performed a complete autopsy, including renal sampling, in HIV-infected adults that died during hospitalization after written informed consent was obtained from the next of kin. Urine was collected postmortem through post-mortem catheterisation or by bladder puncture and tested for LAM with both a lateral flow assay (LFA) and an ELISA assay. Two pathologists assessed the kidney histology. We correlated the LAM-assay results and the histology findings.ResultsOf the 13/36 (36%) patients with a positive urinary LAM ELISA and/or LFA, 8/13 (62%) had renal TB. The remaining 5 LAM-positive patients had disseminated TB without renal involvement. Of the 23 LAM-negative patients, 3 had disseminated TB without renal involvement. The remaining LAM-negative patients had no TB infection and died mostly of fungal and bacterial infections. LAM LFA had a sensitivity of 81% and specificity of 100% to diagnose TB at any location, and the LAM ELISA a sensitivity of 63% and a specificity of 100%. 54% (7/13) LAM LFA-positive patients were not on anti-TB treatment at the time of death.ConclusionRenal TB infection explained LAM-positivity in the majority of patients. Patients with disseminated TB without renal involvement can also be diagnosed with LAM. This suggests that other mechanisms that lead to urinary LAM-positivity exist in a minority of patients.

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Immunoglobulin G subclass responses to mycobacterial lipoarabinomannan in HIV-infected and non-infected patients with tuberculosis

Cited by 36 publications

References 18 publications

Antibodies and tuberculosis

Antibodies and tuberculosis

The Human Antibody Response to the Surface of Mycobacterium tuberculosis

Is Urinary Lipoarabinomannan the Result of Renal Tuberculosis? Assessment of the Renal Histology in an Autopsy Cohort of Ugandan HIV-Infected Adults

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