Skip to main content
Top
Published in: BMC Immunology 1/2019

Open Access 01-12-2019 | Tuberculosis | Research article

IgA and IgG antibody detection of mycobacterial antigens in pleural fluid and serum from pleural tuberculous patients

Authors: Renan Jeremias da Silva, Raquel da Silva Corrêa, Isabela Gama Sardella, Ana Carla de Paulo Mulinari, Thiago Thomaz Mafort, Ana Paula Santos, Rogério Rufino, Luciana Silva Rodrigues, Maria Helena Féres Saad

Published in: BMC Immunology | Issue 1/2019

Login to get access

Abstract

Background

A previous study demonstrated pleural fluid (PF) IgA immunodominance for the fused MT10.3:MPT64 protein in pleural tuberculosis (PLTB) cases. However, no clue on the role of IgA and IgG against this and other antigens in PF and serum concerning improved diagnosis is available. Thus, the aim of the present study was to validate PF IgA-MT10.3:MPT64 and evaluate PF and serum IgA and IgG reactivity against this protein, its peptides (F2) and single MPT64, MT10.3 and the PPE59 mycobacterial specific antigens. IgA and IgG ELISA were measured against the antigen in PLTB (n = 29) and other non-TB pleurisy (n = 39) patient samples.

Results

The immunodominance of PF IgA-MT10.3:MPT64 was confirmed in PLTB (86.2%) followed by PPE59 (62%), while serum IgA-F2 exhibited 51.7% sensitivity. PF and serum IgG-MT10.3:MPT64 led to 65.5 and 51.7% sensitivity, respectively. However, MT10.3 and MPT64 displayed overall lower sensitivity (≤34.5) for both antibodies. All results at 95% fixed specificity. Combinatory results indicated 93.1% sensitivity for PF IgA-MT10.3:MPT64/−PPE59 and IgA/IgG-MT10.3:MPT64 at 92.3% specificity, followed by IgA-MT10.3:MPT64/−MPT64 or /−F2 (89.6%) without jeopardizing specificity (94.9%). The combinatory results of the PF adenosine deaminase test (ADA) and IgA-MT10.3:MPT64/−F2 demonstrated the highest sensitivity (96.6%), with a specificity of 92.3%.

Conclusions

The PF IgA-MT10:MPT64 immune dominance was validated in PLTB, and its combinatory results with PPE59 or MPT64 or F2 antigens as well as with IgG, are reported herein for the first time, improving their potential to assist diagnosis. Combining PF-ADA and IgA-MT10.3:MPT64/−F2 results achieved better accuracy. Moreover, serum IgG, although less accurate, displays potential beyond microbiological tests.
Appendix
Available only for authorised users
Literature
11.
go back to reference Sardella IG, Mulinari ACP, Fonseca LS, Saad MHF. Cloning, expression and characterization of fusion proteins based on peptides of Rv1980c disrupting Rv3019c sequence and evaluation of its potential immunoreactivity in pulmonary tuberculosis sera. Mycobact Disv. 2015. https://doi.org/10.4172/2161-1068.1000183 Sardella IG, Mulinari ACP, Fonseca LS, Saad MHF. Cloning, expression and characterization of fusion proteins based on peptides of Rv1980c disrupting Rv3019c sequence and evaluation of its potential immunoreactivity in pulmonary tuberculosis sera. Mycobact Disv. 2015. https://​doi.​org/​10.​4172/​2161-1068.​1000183
17.
go back to reference Meyer TF, Gibbs CP, Haas R. Variation and control of protein expression in Neisseria. Annu Rev Microbiol. 1990;44:451–77.PubMedCrossRef Meyer TF, Gibbs CP, Haas R. Variation and control of protein expression in Neisseria. Annu Rev Microbiol. 1990;44:451–77.PubMedCrossRef
18.
go back to reference Dheda K, Van Zyl-Smit RN, Sechi LA, Badri M, Meldau R, Meldau S, Symons G, Semple PL, Maredza A, Dawson R, Wainwright H, Whitelaw A, Vallie Y, Raubenheime RP, Bateman ED, Zumla A. Utility of quantitative T-cell responses versus unstimulated interferon-{gamma} for the diagnosis of pleural tuberculosis. Eur Respir J. 2009. https://doi.org/10.1183/09031936.00005309 PubMedCrossRef Dheda K, Van Zyl-Smit RN, Sechi LA, Badri M, Meldau R, Meldau S, Symons G, Semple PL, Maredza A, Dawson R, Wainwright H, Whitelaw A, Vallie Y, Raubenheime RP, Bateman ED, Zumla A. Utility of quantitative T-cell responses versus unstimulated interferon-{gamma} for the diagnosis of pleural tuberculosis. Eur Respir J. 2009. https://​doi.​org/​10.​1183/​09031936.​00005309 PubMedCrossRef
19.
go back to reference Li M, Wang H, Wang X, Huang J, Wang J, Xi X. Diagnostic accuracy of tumor necrosis factor-alpha, interferon-gamma, interleukin-10 and adenosine deaminase 2 in differential diagnosis between tuberculous pleural effusion and malignant pleural effusion. J Cardiothorac Surg. 2014. https://doi.org/10.1186/1749-8090-9-118 Li M, Wang H, Wang X, Huang J, Wang J, Xi X. Diagnostic accuracy of tumor necrosis factor-alpha, interferon-gamma, interleukin-10 and adenosine deaminase 2 in differential diagnosis between tuberculous pleural effusion and malignant pleural effusion. J Cardiothorac Surg. 2014. https://​doi.​org/​10.​1186/​1749-8090-9-118
22.
go back to reference Ogata Y, Aoe K, Hiraki A, Murakami K, Kishino D, Chikamori K, Maeda T, Ueoka H, Kiura K, Tanimoto M. Is adenosine deaminase in pleural fluid a useful marker for differentiating tuberculosis from lung cancer or mesothelioma in Japan, a country with intermediate incidence of tuberculosis? Acta Med Okayama. 2011. https://doi.org/10.18926/AMO/46851. Ogata Y, Aoe K, Hiraki A, Murakami K, Kishino D, Chikamori K, Maeda T, Ueoka H, Kiura K, Tanimoto M. Is adenosine deaminase in pleural fluid a useful marker for differentiating tuberculosis from lung cancer or mesothelioma in Japan, a country with intermediate incidence of tuberculosis? Acta Med Okayama. 2011. https://​doi.​org/​10.​18926/​AMO/​46851.
29.
go back to reference He Y, Zhang W, Huang T, Wang X, Wang M. Evaluation of a diagnostic flow chart applying medical thoracoscopy, adenosine deaminase and T-SPOT.TB in diagnosis of tuberculous pleural effusion. Eur Rev Med Pharmacol Sci. 2015;19:3563–8.PubMed He Y, Zhang W, Huang T, Wang X, Wang M. Evaluation of a diagnostic flow chart applying medical thoracoscopy, adenosine deaminase and T-SPOT.TB in diagnosis of tuberculous pleural effusion. Eur Rev Med Pharmacol Sci. 2015;19:3563–8.PubMed
30.
go back to reference Li D, Shen Y, Fu X, Li M, Wang T, Wen F. Combined detections of interleukin-33 and adenosine deaminase for diagnosis of tuberculous pleural effusion. Int J Clin Exp Pathol. 2015;1:888–93. Li D, Shen Y, Fu X, Li M, Wang T, Wen F. Combined detections of interleukin-33 and adenosine deaminase for diagnosis of tuberculous pleural effusion. Int J Clin Exp Pathol. 2015;1:888–93.
32.
go back to reference Liu Y, Ou Q, Zheng J, Shen L, Zhang B, Weng X, Shao L, Gao Y, Zhang W. A combination of the QuantiFERON-TB gold in-tube assay and the detection of adenosine deaminase improves the diagnosis of tuberculous pleural effusion. Emerg Microbes Infect. 2016. https://doi.org/10.1038/emi.2016.80 Liu Y, Ou Q, Zheng J, Shen L, Zhang B, Weng X, Shao L, Gao Y, Zhang W. A combination of the QuantiFERON-TB gold in-tube assay and the detection of adenosine deaminase improves the diagnosis of tuberculous pleural effusion. Emerg Microbes Infect. 2016. https://​doi.​org/​10.​1038/​emi.​2016.​80
33.
go back to reference Kaisermann M, Sardella IG, Jonas F, Kampfer S, Singh M, Trajmann A, Saad MHF. IgA response to Mycobacterium tuberculosis recombinants MPT64 e MT-10.3 antigens in fluid pleural of patients with tubeculous pleurisy. Int J Tuberc Lung Dis. 2005;9(4):461–6.PubMed Kaisermann M, Sardella IG, Jonas F, Kampfer S, Singh M, Trajmann A, Saad MHF. IgA response to Mycobacterium tuberculosis recombinants MPT64 e MT-10.3 antigens in fluid pleural of patients with tubeculous pleurisy. Int J Tuberc Lung Dis. 2005;9(4):461–6.PubMed
36.
go back to reference Parslow TG. Immunoglobulins & immunoglobulin genes. In: Stites DP, Terr AI, Parslow TG, editors. Medical Immunology. 9th ed. Stamford: Appleton & Lange; 1997. p. 102–42. Parslow TG. Immunoglobulins & immunoglobulin genes. In: Stites DP, Terr AI, Parslow TG, editors. Medical Immunology. 9th ed. Stamford: Appleton & Lange; 1997. p. 102–42.
41.
go back to reference Zhao J, Shiratori B, Okumura M, Yanai H, Matsumoto M, Nakajima C, Mizuno K, Ono K, Oda T, Chagan-Yasutan H, Ashino Y, Matsuba T, Yoshiyama T, Suzuki Y, Hattori T. Difference in antibody responses to Mycobacterium tuberculosis antigens in Japanese tuberculosis patients infected with the Beijing/non-Beijing genotype. J Immunol Res. 2017. https://doi.org/10.1155/2017/4797856 Zhao J, Shiratori B, Okumura M, Yanai H, Matsumoto M, Nakajima C, Mizuno K, Ono K, Oda T, Chagan-Yasutan H, Ashino Y, Matsuba T, Yoshiyama T, Suzuki Y, Hattori T. Difference in antibody responses to Mycobacterium tuberculosis antigens in Japanese tuberculosis patients infected with the Beijing/non-Beijing genotype. J Immunol Res. 2017. https://​doi.​org/​10.​1155/​2017/​4797856
42.
go back to reference Hoff ST, Abebe M, Ravn P, Range N, Malenganisho W, Rodriques DS, Kallas EG, Søborg C, Mark Doherty T, Andersen P, Weldingh K. Evaluation of Mycobacterium tuberculosis--specific antibody responses in populations with different levels of exposure from Tanzania, Ethiopia, Brazil, and Denmark. Clin Infect Dis. 2007. https://doi.org/10.1086/520662 PubMedCrossRef Hoff ST, Abebe M, Ravn P, Range N, Malenganisho W, Rodriques DS, Kallas EG, Søborg C, Mark Doherty T, Andersen P, Weldingh K. Evaluation of Mycobacterium tuberculosis--specific antibody responses in populations with different levels of exposure from Tanzania, Ethiopia, Brazil, and Denmark. Clin Infect Dis. 2007. https://​doi.​org/​10.​1086/​520662 PubMedCrossRef
50.
go back to reference Giusti G, Galanti B. Methods of enzymatic analysis. Weinheim: VerlagChemie; 1984. p. 315. Giusti G, Galanti B. Methods of enzymatic analysis. Weinheim: VerlagChemie; 1984. p. 315.
Metadata
Title
IgA and IgG antibody detection of mycobacterial antigens in pleural fluid and serum from pleural tuberculous patients
Authors
Renan Jeremias da Silva
Raquel da Silva Corrêa
Isabela Gama Sardella
Ana Carla de Paulo Mulinari
Thiago Thomaz Mafort
Ana Paula Santos
Rogério Rufino
Luciana Silva Rodrigues
Maria Helena Féres Saad
Publication date
01-12-2019
Publisher
BioMed Central
Published in
BMC Immunology / Issue 1/2019
Electronic ISSN: 1471-2172
DOI
https://doi.org/10.1186/s12865-019-0315-y

Other articles of this Issue 1/2019

BMC Immunology 1/2019 Go to the issue