IFN-Gamma and IL-2 Secretion after ESAT-6-CFP-10 (EC-610) Fusion Antigen Stimulation from Patients with Active Lung Tuberculosis and Latent Lung Tuberculosis

Bastian Darwin, Nova Kurniati, Kemas Ya'kub Rahadiyanto, Mgs Irsan Saleh, Francisca Srioetami Tanoehardjo, Jusak Nugraha, Eddy Mart Salim

Abstract


The Secretion of IFN-Gamma and IL-2 After ESAT-6-CFP-10 Fusion Antigen Stimulation in Active and Latent TB Patients. This study held to discover how immune responses work and to know the pathogenesis of active TB and latent TB patients. This study used PBMC to stimulate T Cells with ESAT-6 and CFP-10 antigen fusion, and measure the level of IFN-gamma and IL-2 with ELISA antibody sandwich (U-Cytech). 16 ml of blood were drawn to 5 tubes. ESAT-6 CFP-20 inducted one tube with QuantiFERON for IFN-gamma assay. The other four tubes were PBMC isolated using Ficoll-Paque, and pre-incubated with stimulation of ESAT-6 CFP-10 fusion antigen for 24-72 hours at 370 C and measured using T-Spot and ELISA reader. We got from this study that there are no significant differences in IFN-gamma levels for both groups with active TB and latent TB. Measurement of IL-2 levels showed significant differences between the two group.


Keywords


tuberculosis, active TB, latent TB, Elisa antibody

Full Text:

PDF

References


Achmadi, dkk.2005. Pedoman Nasional Penanggulangan Diagnosis. Cetakan kesembilan. Jakarta: Depkes RI 2005.

Abebe F, et al (2017). Association of ESAT6/CFP-10-induced-IFN?, TNF? and IL-10 with clinical tuberculosis: evidence from cohorts of pulmonary tuberculosis patients, household contacts and community controls in an endemic setting. The Journal of Translational Immunology, 189:241-249.

Ahmad S., 2011. Pathogenesis Imunology and diagnosis of laten Mycobacterium tuberculosis infection. Clinical and Developmental Immunolpgy.Volume 11.pp1-17

Ali J., Summer WR., Levitzky MG.2010. Respiratory Infection, In : Pulmonary Pathophysiology 3rd ed. New York : McGraw-Hill, pp 178-181.

Adilistya T. 2016. Manfaat Pemeriksaan Interferon gamma Release Assays untuk diagnosis Tuberkulosis di Indonesia. 43(7):47.33

Adrian R. 2015. Role of cytokin and other factor involved in the Mycobacteriun tuberculosis infection.World Journal of Imunology; 24-25

Aagard, et al. 2004. Mapping Immune Reactivity toward Rv2653 and Rv2654; Two Novel Low-Molecular-Mass Antigen Found Spesifically in The Mycobacterium Complex. Journal of Infectious Disease, 189 (9): 812-818.

Arend SM., Geluk A., van Meijgaarden KE., van Dissel JT., Theisen M., Andersen P., Ottenhoff THM., 2000. Antigenic equivalence of human T-cell responses to Mycobacterium tuberculosis- specifik RD1-encoded protein antigens ESAT-6 and Culture Filtrate Protein 10 and to mixtures of synthetic peptides. Infection and immunity, 68(6),pp.3314-3321.

Betty Agustina Tambunan1, John Wiwin1, Jusak Nugraha1, Soedarsono. 2016. CD4+ Dan CD8+ Interferon Gamma Tuberkulosis Paru Aktif Dan Tuberkulosis Laten. Vol. 22, No. 2 Maret 2016 | Hal. 137–140 p-ISSN 0854-4263 | e-ISSN 4277-4685. Indonesia of journal clinical pathology and medical laboratory

Bratawidjaja K, Rengganis I.2012. Imunologi Dasar Edisi 10. Jakarta: Badan Penerbit FKUI, pp: 399-411

Brodin P., Rosenkrands I., Andersen P., Cole ST., Brosch R., 2004. ESAT-6 Proteins: Protective Antigens and virulence factors? TRENDS in microbiology, 12(11), pp.500-508.

Bapat Prachi R., Husain Aliabhas A., Daginawala Hatim F, et al. 2015. The Assesment of cytikokines in Quantiferon supernatans for The diagnosis of laten TB Infection in tribal population of meghlat. India. Journal of infection and Public Health. Publised by Elsevier Limitide.

Corbiere V. Pottier G. Bonkain F. 2012. Risk stratification of latent tuberculosis defined by combined interferon gamma release assays. Plos One,7:e43285.

Chesov D, Lange C, Daduna F, Crudu V, Preyer R, Ernst M, et al. (2015) Combined Antigen Specific Interferon-? and Interleukin-2 Release Assay (FluoroSpot) for the Diagnosis of Mycobacterium tuberculosis Infection. PloSONE10(3) :e0120006. doi:10.1371/journal.pone.0120006

Champion PAD, Champion MM, Manzanillo P, Cox JS. ESX-1 secreted virulence factors are recognized by multiple cytosolic AAA ATPases in pathogenic mycobacteria. Mol Microbiol. 2009; 73(5): 950-62.

Crofton, S. J. (2002). Tuberkulosis klinis (2 ed.). Jakarta: Widya Medika.

Crevel R., Ottenboff TH., Van der Meer JW. 2002. Innate immunity to Mycobacterium tubercoulsis. Clinical Microbiology reviews. 15(2): 294- 309

Center for Disease Control and Prevention. 2013. Latent Tuberculosis Infection: Guide for Primary Health Care Providers.

Casey, R. et al. (2010). Enumeration of functional T-cell subsets by fluorescence- immunospot defines signatures of pathogen burden in tuberculosis. PLoS One5, e15619

Cellestis Inc.2005. “QuantiFERON-TB” Gold In-Tube package insert.

Dahlan MS., 2012. Besar sampel dan cara pengambilan sampel dalam penelitian kedokteran dan kesehatan Edisi ke-3.Jakarta: Salemba Medika, pp 20-22

Depertemen Kesehatan Republik Indonesia (Depkes RI).2002. Pedoman nasional penanggulangan tuberculosis (cetakan ke-8 ed.). Jakarta: Kementrian Kesehatan RI.

Depertemen Kesehatan Republik Indonesia (Depkes RI).2005. Pedoman Penanggulangan TB Nasional . Depkes RI .Jakarta,2-8.

Depertemen Kesehatan Republik Indonesia (Depkes RI). 2008. Diagnosis & Tatalaksana Tuberkulosis Anak Kelompok Kerja Tb Anak. Depkes-IDAI. Jakarta.

Depertemen Kesehatan Republik Indonesia (Depkes RI).2013. Riset Kesehatan Dasar 2013. Terdapat di :http://www.depkes.go.id. Diakses pada 18 Januari 2018.

Devi A 2012. Hubungan usia, jenis kelamin dan status nutrisi dengan kejadian anemia pada pasien tuberkulosis di RSUP Dr. Kariadi Semarang. Universitas Diponegoro.

Delogu Giovanni.,Michela Sali and Giovanni Fadda .2013 .The Biology of Mycobacterium Tuberculosis Infection. Mediterr J Hematol Infect Dis 2013, 5(1) : e20 13070, DOI: 10.4084/MJHID.2013.070.

El-Sabbagh AM, et al (2016). Interferon-gamma (IFN?) and Interleukin-2 (IL2) as Immunological Markers in Pulmonary Tuberculosis. Journal of Clinical Immunology and Immunopathology Research, 7(1):1-6

European Centre for Disease Prevention and Control (2011). Use of Interferon Gamma Release Assays in Support of TB diagnosis. Stockholm: ECDC

Fitriani, E. 2012. Faktor risiko yang berhubungan dengan kejadian tuberkulosis paru. Unnes Journal of Public Health , 1-7.

Flynn JL. 2001. Immunology of tuberculosis and implication in vaccine development. J Tuberculosis. 84:93-101.

Gyoung HY, Stolinske PG, Smith AB. Combination of Cytokine Responses Indicative of Latent TB and Active TB in Malawian Adults. Plos One. November 2013:8(11).

Gaur RL, Suhosk MM, Banaei N.2012. In Vitro Immunomodulation of a Whole Blood IFN-c Release Assay Enhances T Cell Responses in Subjects with Latent Tuberculosis Infection. PLoS ONE 7(10): e48027. doi:10.1371/journal.pone.0048027.

Hanna BA. 2004. Lobarotory diagnosis. In (Rom WN, Gray SM.eds). Tuberculosisi, 2nd ed. Philadelpia: Lippincott William & Wilkins, pp 163- 175

Handojo I 2003. Pengantar imunoasai dasar. Airlangga University Press. Page 112.

Harari A. Rozot V. Enders FB, et al. 2011. Dominant TNF-? Mycobacterium tuberculosisspesific CD4+ T Cell responses discriminate between latent infection and active disease. Nat Me 17:372-6.

Hermayanti D 2014. Respons imun dan pemeriksaan serologi pada tuberkulosis.Fakultas Kedokteran Universitas Muhammadiyah Malang.

Husain F, dkk. 2010. Pedoman Pencegahan dan Pengendalian Infeksi Diagnosis di Rumah Sakit. Jakarta: Departemen Kesehatan RI.

Husain AA, Daginawala HF, Singh L, and Kashyap RS Current Perspective in Tuberculosis Vaccine.

Hungu.2007. Demografi Kesehatan Indonesia. Jakarta: Grasindo.

Indreswari, S. A., Hadisaputro, S., Soesatyo, M. H., & Handono, K. 2011. Faktor HLA-DRB pada penderita tuberkulosis paru dengan pengobatan strategi DOTS. Media Medika Indonesiana , 45 (1), 34-41.

Jalius 2012. Studi mekanisme interferon dalam pembentukan sistem pertahanan tubuh. Universitas Jambi.

Jawetz, Melnick, Adelberg .2005. Mikrobiologi Kedokteran. Jakarta: Buku Kedokteran EGC, pp: 302-311.

Jordao L. Vieira OV 2011. Tuberculosis : New aspects of an old disease. International Journal of Cell Biology, 1-13.

Jabbar, A., Husain, S., & Khan, A. 2006. Clinical characteristics of pulmonary tuberculosis in adult Pakistani patients with co-existing diabetes mellitus. Eastern Mediterranean Health Journal , 12 (5).

Kusuma C .2007. Diagnostik tuberkulosis paru. Sari Pediatri,Vol 8, No 4,143- 151.

Karuniawati, Risdiyani, Nilawati, Prawoto, Rosana, Alisyahbana, Parwati.Perbandingan Tan Thiam Hok, Zielh Neelsen dan Fluorokrom sebagai metoda Pewarnaan BTA 2005: 29-33.

Kenangalem., and Enny. 2013. The Relationship with Different Body Mass Index Charasteristics Between Papua and Non-Papuan Ethnic Groups. (9): 1-9.

Kemenkes Republik Indonesia 2014. Profil kesehatan Indonesia tahun 2013, Jakarta- Indonesia.

Kim SY, et al (2012). The Responses of Multiple Cytokine Following Incubation of Whole Blood from TB patients, Latently Infected Individuals and Controls with the TB Antigens ESAT-6, CFP-10 and TB7.7. Scandinavian Journal of Immunology, 76:580-585

Lightbody KL, Ilghari D, Waters LC, Carey G, Bailey MA, Williamson RA, et al. Molecular features governing the stability and specificity of functional complex formation by mycobacterium tuberculosis CFP-10/ESAT-6 family proteins. J Biol Chem. 2008; 283 (25):17681-90.

Luo W., et al .2015..Identification of a novel immunodominant antigen Rv2645 from RD13 with potential as a cell-mediated immunity-based TB diagnostic agent. Journal of Infection, 71: 534-543.

Leem A.Y et al (2018). Changes in Cytokine Respones to TB antigens ESAT-6, CFp-10 and TB7.7 and inflammatory Markers in Peripheral Blood During Therapy. Scientific Reports, 8:1159. DOI:10.1038/s41598-018-19523-7

Laal S, Skeiky, YAW .2005. Immune Base Methods. In cole, ST. Eisenach, Kd McMurray, DN, Jacobs. Tuberculosis and The Tubercle Bacillus. ASM Press Washington, DC p71-83

Maderuelo DL, Arnalich F, Serantes R, Gonzales A, Codoceo R, Madero R. Interferon-g and Interleukin-10 Gene Polymorphisms in Pulmonary Tuberculosis. Am J Respir Crit Care Med. 2003;167:970-5.

Movahedi B, Mokarram P, Hemmati M, Mosavari N, Zare R, Safaee Ardekani L, Mostafavi Pour Z (2017). IFN-? and IL-2 Responses to Recombinant AlaDH against ESAT-6/CFP-10 Fusion Antigens in the Diagnosis of Latent versus Active Tuberculosis Infection. Iran J Med Sci. 42(3):275-283.

Mattos, A. M. et al.(2010) Increased IgG1, IFN-gamma, TNF-alpha and IL-6 responses to Mycobacterium tuberculosis antigens in patients with tuberculosis are lower after chemotherapy. Int Immunol22, 775–782

Masniari.2005.Penilaian hasil pengobatan TB paru dan faktor-faktor yang mempengaruhinya serta alasan putus berobat di RS Persahabatan Jakarta. Jurnal Respirologi Indonesia , 25 (1), 1-22.

Mescher LA .2011. Histologi Dasar Junqueira Teks dan Atlas.Jakarta: Buku Kedoktera EGC, pp: 211-214.

Mortaz E., Varahram M., Farnia P., Bahadori M., Masjedi MR., 2012. New aspects in immunopatho.

Notoatmojdo S.2002. Metodologi Kesehatan Edisi Revisi. Jakarta: PT Rineka Cipta, pp: 20-23.

Pedoman Pencegahan dan Pengendalian Infeksi Diagnosis di Rumah Sakit. Jakarta: Departemen Kesehatan RI.

Nugraha J, 2004. Urutan asam amino epitop regio N-Terimun antigen ESAT-6 sebagai marka diagnostik penyakit TB paru aktif . Disertasi. Universitas Airlangga Indonesia.

NCBI. 2010. Pathogenesis, Immunology, and Diagnosis of Latent Mycobacteriumtuberculosis Infection.Available:http://www.ncbi.nlm

.nih.gov/pmc/articles/PMC3017943/figure/fig1/

Oxford Immunotec.2017. T-SPOT.TB Frequently Asked Questions. Oxford Diagnostic Laboratories

Perhimpunan Dokter Paru Indonesia (PDPI).2016. Pedoman Tatalaksana Infeksi TB Laten. Diakses pada tanggal 23 Februari 2018.

Peraturan Menteri Kesehatan Republik Indonesia No 43 Tahun 2013 Tentang Cara Penyelenggaraan Laboratorium Klinik yang Baik. http://labcito.co.id/wpcontent/uploads/2015/ref/ref/PMK_No_43_ttg_Penyel enggaraan_Laboratorium_Klinik_Yang_Baik.pdf. Diakses 12 Februari 2018.

Price, S. A., & Wilson, L. M.2005. Patofisiologi konsep klinis proses-proses penyakit (6 ed., Vol. 2). Jakarta: EGC.

Palomino, J.P, Leao, S.C & Ritacco, P.eds.2007. Tuberkulosis : From basic Science to patien care .(oniline).

Philips JA., Ernts JD.2012. Tuberulosis Pathogenesis and Immunity. Annual Review of Pathology: Mechanisme Of Dissease. Volume 7, pp353-384

Qiagen, .2018. http:// www.quantiferon.com/product/quantiferon-tb-gold- plus/technical-resources/diakses. Diakses pada 01 Febuari 2018

Ravn P, Munk ME, Andersen ÅB, Lundgren B, Lundgren JD, Nielsen LN, et al. Prospective evaluation of a whole - blood test using mycobacterium tuberculosis-specific antigens ESAT-6 and CFP-10 for diagnosis of active tuberculosis. Clin Diagn Lab Immun. 2005;12(4): 491-6.

Raja A.2004. Immunology of tuberculosis. Indian J Med Res. 213-32.

Renshaw PS, Lightbody KL, Veverka V, Muskett FW, Kelly G, Frenkiel TA, et al. Structure and function of the complex formed by the tuberculosis virulence factors CFP-10 and ESAT-6. EMBO Journal. 2005;24:2491-8.

Roostati R .(2008). Analisis kadar interferon gamma pada penderita tuberkulosis paru dan bukan penderita tuberkulosis.Universitas Sumatera Utara.

Sacher, R. A., & McPherson, R. A.2004. Tinjauan klinis hasil pemeriksaan sistem laboratorium (11 ed.). Jakarta: EGC.

Sanusi, H. (2003). Diabetes melitus tipe II pada TB paru . Makasar: Perhimpunan Dokter Paru Indonesia

Setiawan H., Nugraha J.2016. Analisis IFN-? dan IL-10 pada PMBC Penderita Tuberkulosis Aktif, Laten dan Orang Sehat setelah distimulasi Antigen ESAT-6. Universitas Airlangga. Surabaya.

Sinaga H.2011. Isolasi dan Identifikasi Mycobacterium Tuberculoss Untuk Petugas Laboratorium. Palembang: Multi Sarana, pp: 5-59.

Smeltzer, S. C., & Bare, B. G. 2001. Buku ajar keperawatan medikal bedah Brunner& Suddarth (8 ed., Vol. 1). Jakarta: EGC.

Schwander S, Dheda K. 2007. Human lung immunity againts mycobacteriun tuberculosis.J Clini Immunol;27(4).347-62

Soedarto .1996. Penyakit-Penyakit Infeksi Di Indonesia. Jakarta: Widya Medika, pp: 179-183. Husain F, dkk (2010).

Theel E.S, et al (2018). Comparison of the QuantiFERON-TB Gold Plus and QuantiFERON-TB Gold In-Tube Interferon Gamma Release Assays in Patients at Risk for Tuberculosis and in Health Care Workers. Journal of Clinical Microbiology American Society for Microbiology, 56 (7): 1-12

Van Pinxteren LAH., Ravn P., Agger EM. Et al, 2000. Diagnosis of tuberculosis based on the two specific antigens ESAT-6 and CFP10. Clinical and Diagnostic Laboratory Immunology, 7(2), pp.155-160.

Underwood, J. (2000). Patologi umum dan sistematik (2 ed.). Jakarta: EGC. Walsh M. (2013). Infection Landscap: Tuberculosis diakses tanggal 3 februari 2018.

Walz G.,Ronacher K.,HanekomW.,Scriba TJ.,Zumia A.,(2011). Imunological biomakers of tuberculosis. Nature Reviews Imunology,Volume 11,pp.343- 354

Wellin.A.(2011). Survival Strategis of Mycobacterium tuberculosis inside the human Macrophage. Lingkoping University Medical Dissertations. LiU Tryck. Linkoping.12-15.

WHO. (2015). Tuberculosis. Diunduh di http://www.who.int/mediacentre/factsh eets/fs104/en/ pada tanggal 02 Februari 2018.

WHO. (2016). Global Tuberculosis Report 2016. Geneva:WHO Press. Pp1-35

Wang S, et al. (2012). Evaluation of the Diagnostic Potential of IP-10 and IL-2 as Biomarkers for the Diagnosis of Active and Latent Tuberculosis in a BCG- Vaccinated Population. PLoS ONE 7(12): e51338. doi:10.1371/journal.pone.0051338

Widjaja T .(2011). Infeksi Laten Tuberkulosis : Keseimbangan antara sistem imun pejamu dan strategi bertahan M. tuberculosis. Pulmonologi Fakultas Kedokteran Universitas Kristen Maranatha, RS Immanuel Bandung Indonesia. Continuing Medical Education 183/vol 38 no2.

Widjaja T. Jasaputra D. Roostati R.(2010). Analisis kadar interferon gamma pada penderita tuberkulosis paru dan orang sehat. FK Universitas Kristen Maranatha. J Respir. Vol 302.No2

Zhang J. Chen Y.(2011). Interleukin-10 polymorphisms and tuberculosis susceptibilit meta-analysis. Int J Tuberc Lung Dis.15(5):594-601.doi:10.5588/ijtld.09.0703




DOI: https://doi.org/10.32539/bji.v6i2.10741

Refbacks

  • There are currently no refbacks.


Editorial Office
Fakultas Kedokteran Universitas Sriwijaya
OJS: http:ejournal.unsri.ac.id/index.php/bji
Email: biomedicaljournalindonesia@gmail.com
CP: Admin 

Creative Commons License
Biomedical Journal of Indonesia: Jurnal Biomedik Fakultas Kedokteran Universitas Sriwijaya by https://ejournal.unsri.ac.id/index.php/bji is licensed under a Creative Commons Attribution-ShareAlike 4.0 International License.