IL-18/IL-37/IP-10 Signalling Complex As a Potential Biomarker for Discriminating Active and Latent TB

Overview

Journal PLoS One

Specialties General Medicine
Science

Date 2019 Dec 11

PMID 31821340

Citations 13

Authors

Sebastian Wawrocki

Michal Seweryn

Grzegorz Kielnierowski

Wieslawa Rudnicka

Marcin Wlodarczyk

Magdalena Druszczynska

Affiliations

Soon will be listed here.

Abstract

Background: Currently, there are serious limitations in the direct diagnosis of active tuberculosis (ATB). We evaluated the levels of the IL-18/IL-37/IP-10 signalling complex proteins in Mycobacterium tuberculosis (M.tb)-specific antigen-stimulated QuantiFERON® Gold In-Tube (QFT) cultures and in serum samples from ATB patients, healthy individuals with latent M.tb infection (LTBI) and healthy controls (HC) to examine whether combined analyses of these proteins were useful in the differentiation of M.tb states.

Methods: The concentrations of IL-18, IL-18BP, IFN-γ, IL-37 and IP-10 in the serum and QFT supernatants were measured using specific enzyme-linked immunosorbent assay (ELISA) kits. Free IL-18 levels were calculated using the law of mass action.

Results: Increased concentrations of total and free IL-18, IL-18BP, IFN-γ and IP-10 in the sera of ATB patients were detected. These increases were not counterbalanced by the overproduction of IL-37. Complex co-expression of serum IL-18BP and IL-37, IP-10 and IFN-γ was identified as the highest discriminative biomarker set for the diagnosis of ATB.

Conclusions: Our results suggest that the IL-18 signalling complex might be exploited by M. tuberculosis to expand the clinical manifestations of pulmonary TB. Therefore, direct analysis of the serum components of the IL-18/IL-37 signalling complex and IP-10 may be applicable in designing novel diagnostic tests for ATB.

Citing Articles

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References

Barksby H, Lea S, Preshaw P, Taylor J . The expanding family of interleukin-1 cytokines and their role in destructive inflammatory disorders. Clin Exp Immunol. 2007; 149(2):217-25. PMC: 1941943. DOI: 10.1111/j.1365-2249.2007.03441.x. View

Banda N, Vondracek A, Kraus D, Dinarello C, Kim S, Bendele A . Mechanisms of inhibition of collagen-induced arthritis by murine IL-18 binding protein. J Immunol. 2003; 170(4):2100-5. DOI: 10.4049/jimmunol.170.4.2100. View

Goyal N, Kashyap B, Kaur I . Significance of IFN-ɤ/IL-2 Ratio as a Circulating Diagnostic Biomarker in Extrapulmonary Tuberculosis. Scand J Immunol. 2016; 83(5):338-44. DOI: 10.1111/sji.12424. View

Dinarello C, Nold-Petry C, Nold M, Fujita M, Li S, Kim S . Suppression of innate inflammation and immunity by interleukin-37. Eur J Immunol. 2016; 46(5):1067-81. PMC: 5003108. DOI: 10.1002/eji.201545828. View

Weiner J, Kaufmann S . High-throughput and computational approaches for diagnostic and prognostic host tuberculosis biomarkers. Int J Infect Dis. 2016; 56:258-262. DOI: 10.1016/j.ijid.2016.10.017. View

La Manna M, Orlando V, Li Donni P, Sireci G, Di Carlo P, Cascio A . Identification of plasma biomarkers for discrimination between tuberculosis infection/disease and pulmonary non tuberculosis disease. PLoS One. 2018; 13(3):e0192664. PMC: 5854242. DOI: 10.1371/journal.pone.0192664. View

Migliorini P, Anzilotti C, Pratesi F, Quattroni P, Bargagna M, Dinarello C . Serum and urinary levels of IL-18 and its inhibitor IL-18BP in systemic lupus erythematosus. Eur Cytokine Netw. 2010; 21(4):264-71. DOI: 10.1684/ecn.2010.0210. View

Chegou N, Sutherland J, Malherbe S, Crampin A, Corstjens P, Geluk A . Diagnostic performance of a seven-marker serum protein biosignature for the diagnosis of active TB disease in African primary healthcare clinic attendees with signs and symptoms suggestive of TB. Thorax. 2016; 71(9):785-94. DOI: 10.1136/thoraxjnl-2015-207999. View

Kunnath-Velayudhan S, Gennaro M . Immunodiagnosis of tuberculosis: a dynamic view of biomarker discovery. Clin Microbiol Rev. 2011; 24(4):792-805. PMC: 3194832. DOI: 10.1128/CMR.00014-11. View

10.

Takenami I, Loureiro C, Machado Jr A, Emodi K, Riley L, Arruda S . Blood Cells and Interferon-Gamma Levels Correlation in Latent Tuberculosis Infection. ISRN Pulmonol. 2013; 2013. PMC: 3769793. DOI: 10.1155/2013/256148. View

11.

Kim S, Eisenstein M, Reznikov L, Fantuzzi G, Novick D, Rubinstein M . Structural requirements of six naturally occurring isoforms of the IL-18 binding protein to inhibit IL-18. Proc Natl Acad Sci U S A. 2000; 97(3):1190-5. PMC: 15564. DOI: 10.1073/pnas.97.3.1190. View

12.

Vankayalapati R, Wizel B, Weis S, Samten B, Girard W, Barnes P . Production of interleukin-18 in human tuberculosis. J Infect Dis. 2000; 182(1):234-9. DOI: 10.1086/315656. View

13.

Yamada G, Shijubo N, Shigehara K, Okamura H, Kurimoto M, Abe S . Increased levels of circulating interleukin-18 in patients with advanced tuberculosis. Am J Respir Crit Care Med. 2000; 161(6):1786-9. DOI: 10.1164/ajrccm.161.6.9911054. View

14.

Wassie L, Demissie A, Aseffa A, Abebe M, Yamuah L, Tilahun H . Ex vivo cytokine mRNA levels correlate with changing clinical status of ethiopian TB patients and their contacts over time. PLoS One. 2008; 3(1):e1522. PMC: 2211401. DOI: 10.1371/journal.pone.0001522. View

15.

Bufler P, Azam T, Gamboni-Robertson F, Reznikov L, Kumar S, Dinarello C . A complex of the IL-1 homologue IL-1F7b and IL-18-binding protein reduces IL-18 activity. Proc Natl Acad Sci U S A. 2002; 99(21):13723-8. PMC: 129755. DOI: 10.1073/pnas.212519099. View

16.

Chegou N, Black G, Loxton A, Stanley K, Essone P, Klein M . Potential of novel Mycobacterium tuberculosis infection phase-dependent antigens in the diagnosis of TB disease in a high burden setting. BMC Infect Dis. 2012; 12:10. PMC: 3282638. DOI: 10.1186/1471-2334-12-10. View

17.

Wlodarczyk M, Rudnicka W, Janiszewska-Drobinska B, Kielnierowski G, Kowalewicz-Kulbat M, Fol M . Interferon-gamma assay in combination with tuberculin skin test are insufficient for the diagnosis of culture-negative pulmonary tuberculosis. PLoS One. 2014; 9(9):e107208. PMC: 4164613. DOI: 10.1371/journal.pone.0107208. View

18.

Hartmann K, Seweryn M, Handelman S, Rempala G, Sadee W . Non-linear interactions between candidate genes of myocardial infarction revealed in mRNA expression profiles. BMC Genomics. 2016; 17(1):738. PMC: 5027110. DOI: 10.1186/s12864-016-3075-6. View

19.

Szpakowski P, Biet F, Locht C, Paszkiewicz M, Rudnicka W, Druszczynska M . Dendritic Cell Activity Driven by Recombinant Mycobacterium bovis BCG Producing Human IL-18, in Healthy BCG Vaccinated Adults. J Immunol Res. 2015; 2015:359153. PMC: 4539176. DOI: 10.1155/2015/359153. View

20.

El-Masry S, Lotfy M, Nasif W, El-Kady I, Al-Badrawy M . Elevated serum level of interleukin (IL)-18, interferon (IFN)-gamma and soluble Fas in patients with pulmonary complications in tuberculosis. Acta Microbiol Immunol Hung. 2007; 54(1):65-77. DOI: 10.1556/AMicr.54.2007.1.7. View