Evaluation of Humoral Immunity to<i>Mycobacterium tuberculosis</i>-Specific Antigens for Correlation with Clinical Status and Effective Vaccine Development

Niki, Mamiko; Suzukawa, Maho; Akashi, Shunsuke; Nagai, Hirokazu; Ohta, Ken; Inoue, Matsuhisa; Kaneko, Yukihiro; Morimoto, Kozo; Kurashima, Atsuyuki; Kitada, Shuichi; Matsumoto, Sohkichi; Suzuki, Koichi; Hoshino, Yoshihiko

doi:10.1155/2015/527395

Cited by 23 publications

(38 citation statements)

References 60 publications

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“…IgA against HrpA associated with improved severity markers on presentation in active TB disease [40]…”

Section: Figurementioning

confidence: 99%

“…The presence of IgG against Ag85A has elsewhere been associated with decreased cavitation and a greater chance of sputum clearance of M.tb in a cohort of Mexican patients [38] The development of clinically defined AIDS is associated with waning antibody titres against M.tb antigens in purified protein derivative (PPD) – suggesting that the risk for severe disease in this population may not be exclusively due to loss of CD4 + cells [39]. IgA against α–crystallin (Acr) and HrpA are associated with improved markers of disease severity at the time of admission, with lower albumin and CRP levels seen in patients with higher titres of antibodies against these antigens [40]. These findings suggest that a vaccine eliciting such antibodies may prevent extrapulmonary TB and thus reduce mortality and morbidity from TB.…”

Section: Introductionmentioning

confidence: 99%

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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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“…IgA against HrpA associated with improved severity markers on presentation in active TB disease [40]…”

Section: Figurementioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Antibodies and tuberculosis

et al. 2016

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“…A combination of antigen and adjuvant molecules can influence antigen-stimulated T cell cytokine profiles (11). Studies have demonstrated an inverse correlation between Th1-type hypersensitivity to M. tuberculosis and atopy in Japanese school children, and heat-killed or live Mycobacteria down-regulate Th2 responses to allergens (12,13). Consistent with this finding, another study has investigated using preparations of non-pathogenic M. vaccae in prophylactic treatment of allergic inflammation and asthma in murine models (14).…”

Section: Discussionmentioning

confidence: 89%

Intranasal ovalbumin immunotherapy with mycobacterial adjuvant promotes regulatory T cell accumulation in lung tissues

Akkoç

Genç

Zibandeh

et al. 2018

Microbiology and Immunology

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Allergen-specific immunotherapy to induce T regulatory cells in the periphery has been used to treat allergic diseases. Mycobacteria can be used as an adjuvant for inducing T regulatory cells. However, it is unclear whether intranasal immunotherapy in combination with Mycobacteria adjuvant induces regulatory T cell differentiation and attenuates allergic responses in vivo. To investigate the role of intranasal ovalbumin (OVA) treatment alone and in combination with Mycobacteria vaccae, proportions of FoxP3 regulatory T cells and anti-inflammatory responses were evaluated in a murine model of asthma that was established in three groups of bicistronic Foxp3 reporter BALB/c mice. Before establishment of the asthma model, two groups of mice received intranasal OVA immunotherapy and one also received simultaneous s.c. M. vaccae. Expression of CD4 CD25 Foxp3 T cells in the lung and spleen was analyzed by flow cytometry and the cytokine profiles of allergen-stimulated lung and spleen lymphocytes assessed. The intranasal OVA immunotherapy group showed greater expression of CD4 CD25 Foxp3 T cells in the spleen whereas in the group that also received M. vaccae such greater expression was demonstrated in the lung. Additionally, the proportion of IL-10 and IFN-γ-secreting splenocytes was greater in the intranasal OVA + M. vaccae group. CD25 neutralization decreased CD4 Foxp3 cells more than other groups. In parallel with this finding, production of IL-10 and IFN-γ was down-regulated. Mucosal administration of OVA antigen results in a greater proportion of CD4 Foxp3 T cells in the spleen. IL-10 and IFN-γ induced by intranasal OVA immunotherapy and M. vaccae administration is down-regulated after CD25 neutralization.

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“…While IgA-HrpA levels correlated signi cantly with active TB, the IgA-16 kDa/ESAT6 was signi cantly associated with the nutritional status of the participants. Others reported IgA anti-mycobacterial antigens HrpA and MDP1 higher response among controls than in TB patients suggesting that different stress on bacterium and host modulates proteomic expression, and the IgA immune response may be protective [31]. Williams et al (2004) reported IgA against the 16 kDa α-cristalin mediated some protection against TB, as evidenced by reduced mycobacterial burden in the lungs [32].…”

Section: Discussionmentioning

confidence: 99%

PPE 59 immunoreactivity in tuberculosis patients: IgA immunodominance to that IgG and IgM

Mulinari¹,

Sardella²,

Silva³

et al. 2020

Preprint

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Background: The role of protein families PE/PPE remains relatively enlightening. The gene rv3429, coding the PPE59 protein, is one of the 12 members of the PPE subfamily, and it is absent in all BCG strains. Although elicits low T cell response, there are no clues for the ability to induce a humoral response. Methods: We cloned, expressed, and analyzed by ELISA IgG, IgM and IgA anti PPE59 in 212 sera. Of them, 69 were from tuberculosis patients’ residents in Italy (TBIT, 12 native and 67 immigrants), the remaining 133 are Brazilians citizens (BR). Pulmonary (pTBIT) or extrapulmonary (eTBIT) clinical forms were 54 or 25. The pTBBR were 52 and 81 non-TB patients, including 10 non-tuberculous mycobacteria infected (NTM). Results: Keeping the specificity at 97%, IgA sensitivity decreased from pTBBR (53%) to pTBIT (38%) and eTBIT (28%), with an overall sensitivity of 42.7% and moderate accuracy (61.8 %), while IgG showed significant lower (p<0.0001) performance, 21%, 3%, 0%, 9% and 37%, respectively, at specificity of 83%. Groups were not discriminate by IgM. False-positive NTM IgG was high. Combination 16kDa IgG, previously performed only on Bazilians’ sera, plus PPE 59 IgA results increased sensitivity to 71% at 87.4% specificity. The overall smear microscopy (SM) diagnosis was 70.8% and a combination of SM/IgA increased sensitivity to 74% (p=0.01), mainly among SM- cases. Among pTBBR, all these rapid tests, including SM, sensitivity reach 86.5% (p=0.001). Positive IgA polarization was significant in extensive lung disease (p=0.001) and alcohol users (p=0.04). Conclusion: Although PPE59 IgA independently has moderate accuracy on TB diagnosis, together with other biomarkers contributes to improving its detection. Moreover, the polarized reactivity deserves further investigation.

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Evaluation of Humoral Immunity toMycobacterium tuberculosis-Specific Antigens for Correlation with Clinical Status and Effective Vaccine Development

Cited by 23 publications

References 60 publications

Antibodies and tuberculosis

Antibodies and tuberculosis

Intranasal ovalbumin immunotherapy with mycobacterial adjuvant promotes regulatory T cell accumulation in lung tissues

PPE 59 immunoreactivity in tuberculosis patients: IgA immunodominance to that IgG and IgM

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