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Protein & Peptide Letters

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ISSN (Print): 0929-8665
ISSN (Online): 1875-5305

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Research Article

Diagnostic Accuracy of Monocyte Chemotactic Protein (MCP)-2 as Biomarker in Response to PE35/PPE68 Proteins: A Promising Diagnostic Method for the Discrimination of Active and Latent Tuberculosis

Author(s): Setareh Mamishi, Babak Pourakbari, Reihaneh Hosseinpour Sadeghi, Majid Marjani and Shima Mahmoudi*

Volume 26, Issue 4, 2019

Page: [281 - 286] Pages: 6

DOI: 10.2174/0929866526666190119165805

Price: $65

Abstract

Introduction: Several studies have been conducted to find new biomarkers for the discrimination of Latent Tuberculosis Infection (LTBI) from active TB (ATB); however, their findings are inconsistent. The aim of the current study was to evaluate the potential of in vitro antigenspecific expression of Monocyte Chemotactic Protein (MCP)-2 for discrimination of ATB and LTBI after stimulation of whole blood with PE35 and PPE68 recombinant proteins.

Materials and Methods: The recombinant PE35 and PPE68 proteins were evaluated at a final concentration of 5 µg/ml by a 3-day whole blood assay. Secreted MCP-2 from the culture supernatants were measured by commercially available Human MCP2 ELISA Kit. The diagnostic performance of MCP-2 was ascertained by Receiver Operator Characteristic (ROC) curve and measuring the Area Under the Curve (AUC) and their 95% confidence intervals (CI). Cut-offs was estimated at various sensitivities and specificities and at the maximum Youden’s index (YI), i.e. sensitivity specificity–1.

Results: The median MCP-2 response to both PE35 and PPE68 in those with LTBI was significantly higher than patients with ATB. The discrimination performance of MCP-2 response following stimulation of PE35 (assessed by AUC) between LTBI and patients with ATB was 0.98 (95%CI: 0.94-1.00). Maximum discrimination was reached at a cut-off of 86pg/mL with 100% sensitivity and 97% specificity. The highest sensitivity and specificity was obtained using cut off 58 pg/mL following stimulation with PPE68 (100% and 90%, respectively; AUC: 0.94, 95%CI: 0.85- 1.00).

Conclusion: MCP-2 induced by PE35 and PPE68 shows good discriminatory power for discrimination of ATB and LTBI. Additional studies with a larger sample size are needed to confirm the advantage of this marker, alone or combined with other markers; however, these findings present a promising method, which can discriminate between ATB and LTBI.

Keywords: MCP-2, PE35, PPE68, active tuberculosis, latent tuberculosis, monocyte chemotactic protein.

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Graphical Abstract

[1]
World Health Organization. Global tuberculosis report 2016. 2016.
[2]
Barry, (III), C.E.; Boshoff, H.I.; Dartois, V.; Dick, T.; Ehrt, S.; Flynn, J.; Schnappinger, D.; Wilkinson, R.J.; Young, D. The spectrum of latent tuberculosis: Rethinking the biology and intervention strategies. Nat. Rev. Microbiol., 2009, 7(12), 845-855.
[3]
Mahmoudi, S.; Mamishi, S.; Ghazi, M.; Sadeghi, R.H.; Pourakbari, B. Cloning, expression and purification of Mycobacterium tuberculosis ESAT-6 and CFP-10 antigens. Iran. J. Microbiol., 2013, 5(4), 374-378.
[4]
Mamishr, S.; Pourakbari, B.; Marjani, M.; Mahmoudi, S. Diagnosis of latent tuberculosis infection among immunodeficient individuals: Review of concordance between interferon-gamma release assays and the tuberculin skin test. Br. J. Biomed. Sci., 2014, 71(3), 115-124.
[5]
John, S.H.; Kenneth, J.; Gandhe, A.S. Host biomarkers of clinical relevance in tuberculosis: Review of gene and protein expression studies. Biomarkers, 2012, 17(1), 1-8.
[6]
Pai, M.; Zwerling, A.; Menzies, D. Systematic review: T-Cell–based assays for the diagnosis of latent tuberculosis infection: An update T-Cell–based assays for the diagnosis of latent tuberculosis infection. Ann. Intern. Med., 2008, 149(3), 177-184.
[7]
Mamishi, S.; Pourakbari, B.; Teymuri, M.; Rubbo, P.A.; Tuaillon, E.; Keshtkar, A.A.; Mahmoudi, S. Diagnostic accuracy of IL-2 for the diagnosis of latent tuberculosis: A systematic review and meta-analysis. Eur. J. Clin. Microbiol. Infect. Dis., 2014, 33(12), 2111-2119.
[8]
Pathakumari, B.; Prabhavathi, M.; Raja, A. Evaluation of cytokine and chemokine response elicited by Rv2204c and Rv0753c to detect latent tuberculosis infection. Cytokine, 2015, 76(2), 496-504.
[9]
Keshavarz Valian, S.; Mahmoudi, S.; Pourakbari, B.; Abdolsalehi, M.R.; Eshaghi, H.; Mamishi, S. Screening of healthcare workers for latent tuberculosis infection in the low tuberculosis burden country: QuantiFERON-TB gold in tube test or tuberculin skin test? Arch. Environ. Occup. Health, 2018, 1-6.
[10]
Basera, T.J.; Ncayiyana, J.; Engel, M.E. Prevalence and risk factors of latent tuberculosis infection in Africa: A systematic review and meta-analysis protocol. BMJ Open, 2017, 7(7), e012636.
[11]
De Groote, M.A.; Higgins, M.; Hraha, T.; Wall, K.; Wilson, M.L.; Sterling, D.G.; Janjic, N.; Reves, R.; Ochsner, U.A. Belknap R highly multiplexed proteomic analysis of quantiferon supernatants to identify biomarkers of latent tuberculosis infection. J. Clin. Microbiol., 2017, 55(2), 391-402.
[12]
Goletti, D.; Raja, A.; Kabeer, B.S.; Rodrigues, C.; Sodha, A.; Butera, O.; Carrara, S.; Vernet, G.; Longuet, C.; Ippolito, G.; Thangaraj, S. IFN-gamma, but not IP-10, MCP-2 or IL-2 response to RD1 selected peptides associates to active tuberculosis. J. Infect., 2010, 61(2), 133-143.
[13]
Liu, H.; Liu, Z.; Chen, J.; Chen, L.; He, X.; Zheng, R.; Yang, H.; Song, P.; Weng, D.; Hu, H.; Fan, L. Induction of CCL8/MCP-2 by mycobacteria through the activation of TLR2/PI3K/Akt signaling pathway. PLoS One, 2013, 8(2), e56815.
[14]
Mamishi, S.; Pourakbari, B.; Marjani, M.; Bahador, A.; Mahmoudi, S. Discriminating between latent and active tuberculosis: The role of interleukin-2 as biomarker. J. Infect., 2015, 70(4), 429-431.
[15]
Ruhwald, M.; Bodmer, T.; Maier, C. Evaluating the potential of IP-10 and MCP-2 as biomarkers for the diagnosis of tuberculosis. Eur. Respir. J., 2008, 32(6), 1607-1615.
[16]
Kunnath-Velayudhan, S.; Gennaro, M.L. Immunodiagnosis of tuberculosis: A dynamic view of biomarker discovery. Clin. Microbiol. Rev., 2011, 24(4), 792-805.
[17]
Mamishi, S.; Pourakbari, B.; Shams, H.; Marjani, M.; Mahmoudi, S. Improving T-cell assays for diagnosis of latent TB infection: Confirmation of the potential role of testing Interleukin-2 release in Iranian patients. Allergol. Immunopathol. (Madr.), 2016, 44(4), 314-321.
[18]
Gong, X.; Gong, W.; Kuhns, D.B.; Ben-Baruch, A.; Howard, O.M.; Wang, J.M. Monocyte Chemotactic Protein-2 (MCP-2) uses CCR1 and CCR2B as its functional receptors. J. Biol. Chem., 1997, 272(18), 11682-11685.
[19]
Abdallah, A.M.; Gey van Pittius, N.C.; Champion, P.A.; Cox, J.; Luirink, J.; Vandenbroucke-Grauls, C.M.; Appelmelk, B.J.; Bitter, W. Type VII secretion-mycobacteria show the way. Nat. Rev. Microbiol., 2007, 5(11), 883-891.
[20]
Tiwari, B.; Soory, A.; Raghunand, T.R. An immunomodulatory role for the Mycobacterium tuberculosis region of difference 1 locus proteins PE35 (Rv3872) and PPE68 (Rv3873). FEBS J., 2014, 281(6), 1556-1570.
[21]
Mahmoudi, S.; Pourakbari, B.; Mamishi, S. Interferon gamma release assay in response to PE35/PPE68 proteins: A promising diagnostic method for diagnosis of latent tuberculosis. Eur. Cytokine Netw., 2017, 28(1), 36-40.
[22]
Pourakbari, B.; Mamishi, S.; Marjani, M.; Rasulinejad, M.; Mariotti, S.; Mahmoudi, S. Novel T-cell assays for the discrimination of active and latent tuberculosis infection: the diagnostic value of PPE family. Mol. Diagn. Ther., 2015, 19(5), 309-316.
[23]
Youden, W.J. Index for rating diagnostic tests. Cancer, 1950, 3(1), 32-35.
[24]
Goletti, D.; Raja, A.; Kabeer, S.A.B.; Rodrigues, C.; Sodha, A.; Carrara, S.; Vernet, G.; Longuet, C.; Ippolito, G.; Thangaraj, S.; Leportier, M.; Girardi, E.; Lagrange, P.H. Is IP-10 an accurate marker for detecting M. tuberculosis-specific response in HIV-infected persons? PLoS One, 2010, 5(9), e12577.
[25]
Nonghanphithak, D.; Reechaipichitkul, W.; Namwat, W.; Naranbhai, V.; Faksri, K. Chemokines additional to IFN-gamma can be used to differentiate among Mycobacterium tuberculosis infection possibilities and provide evidence of an early clearance phenotype. Tuberculosis (Edinb.), 2017, 105, 28-34.
[26]
Biraro, I.A.; Kimuda, S.; Egesa, M.; Cose, S.; Webb, E.L.; Joloba, M.; Smith, S.G.; Elliott, A.M.; Dockrell, H.M.; Katamba, A. The use of interferon gamma inducible protein 10 as a potential biomarker in the diagnosis of latent tuberculosis infection in Uganda. PLoS One, 2016, 11(1), e0146098.
[27]
Jeong, Y.H.; Hur, Y.G.; Lee, H.; Kim, S.; Cho, J.E.; Chang, J.; Shin, S.J.; Lee, H.; Kang, Y.A.; Cho, S.N.; Ha, S.J. Discrimination between active and latent tuberculosis based on ratio of antigen-specific to mitogen-induced IP-10 production. J. Clin. Microbiol., 2015, 53(2), 504-510.
[28]
Chegou, N.N.; Heyckendorf, J.; Walzl, G.; Lange, C.; Ruhwald, M. Beyond the IFN-γ horizon: biomarkers for immunodiagnosis of infection with Mycobacterium tuberculosis. Eur. Respir. J., 2014, 43(5), 1472-1486.
[29]
Goletti, D.; Carrara, S.; Vincenti, D.; Saltini, C.; Rizzi, E.B.; Schininà, V.; Ippolito, G.; Amicosante, M.; Girardi, E. Accuracy of an immune diagnostic assay based on RD1 selected epitopes for active tuberculosis in a clinical setting: A pilot study. Clin. Microbiol. Infect., 2006, 12(6), 544-550.
[30]
Pokkali, S.; Das, S.D. Augmented chemokine levels and chemokine receptor expression on immune cells during pulmonary tuberculosis. Hum. Immunol., 2009, 70(2), 110-115.

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