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Analysis of Immune Responses against a Wide Range of Mycobacterium tuberculosis Antigens in Patients with Active Pulmonary Tuberculosis

Analysis of Immune Responses against a Wide Range of Mycobacterium tuberculosis Antigens in... Analysis of Immune Responses against a Wide Range of Mycobacterium tuberculosis Antigens in Patients with Active Pulmonary Tuberculosis Desta Kassa a , b , Leonie Ran b , Wudneh Geberemeskel a , Mekashaw Tebeje a , Amelewerk Alemu a , Alemayehu Selase c , Belete Tegbaru a , Kees L. M. C. Franken d , Annemieke H. Friggen d , Krista E. van Meijgaarden d , Tom H. M. Ottenhoff d , Dawit Wolday e , Tsehaynesh Messele a and Debbie van Baarle b a Infectious and Noninfectious Diseases Research Directorate, Ethiopian Health and Nutrition Research Institute (EHNRI), Addis Ababa, Ethiopia b Department of Internal Medicine and Infectious Diseases and Department of Immunology, University Medical Center Utrecht, Utrecht, The Netherlands c St Peter Specialized TB Hospital, Addis Ababa, Ethiopia d Department of Infectious Diseases, Leiden University Medical Center, Leiden, The Netherlands e Medical Biotech Laboratory, Addis Ababa, Ethiopia ABSTRACT Characterizing host immune responses to molecular targets of Mycobacterium tuberculosis is essential to develop effective immunodiagnostics and better vaccines. We investigated the immune response against a large series of M. tuberculosis antigens, including 5 classical and 64 nonclassical (39 DosR regulon-encoded, 4 resuscitation-promoting factor (RPF), and 21 reactivation-associated) antigens in active-pulmonary-tuberculosis (TB) patients. Whole blood from TB patients ( n = 34) was stimulated in vitro with M. tuberculosis antigens. Gamma interferon (IFN-γ) was measured after 7 days of stimulation, using an enzyme-linked immunosorbent assay (ELISA). The majority of the study participants responded to the classical M. tuberculosis antigens TB10.4 (84.8%), early secreted antigenic target-6 kDa (ESAT-6)/CFP-10 (70.6%), and purified protein derivative (PPD) (55.9%). However, only 26.5% and 24.2% responded to HSP65 and Ag85A/B, respectively. Of the 64 nonclassical antigens, 23 (33.3%) were immunogenic (IFN-γ levels, >62 pg/ml) and 8 were strong inducers of IFN-γ (IFN-γ levels, ≥100 pg/ml). The RPF antigens were the most immunogenic. In addition, we observed distinct cytokine expression profiles in response to several M. tuberculosis antigens by multiplex immunoassay. Tumor necrosis factor alpha (TNF-α), interleukin 10 (IL-10), and IL-6 were commonly detected at high levels after stimulation with 4/15 latency antigens (Rv0081, Rv2006, Rv2629, and Rv1733c) and were found especially in supernatants of the three strong IFN-γ inducers (Rv2629, Rv1009, and Rv2389c). IL-8, IL-6, and IL-17 were exclusively detected after stimulation with Rv0574c, Rv2630, Rv1998, Rv054c, and Rv2028c. In conclusion, in active-pulmonary-TB patients, we identified 23 new immunogenic M. tuberculosis antigens. The distinct expression levels of IFN-γ, TNF-α, IL-6, and IL-10 in response to specific subsets of M. tuberculosis antigens may be promising for the development of immunodiagnostics. http://www.deepdyve.com/assets/images/DeepDyve-Logo-lg.png Clinical and Vaccine Immunology American Society For Microbiology

Analysis of Immune Responses against a Wide Range of Mycobacterium tuberculosis Antigens in Patients with Active Pulmonary Tuberculosis

Clinical and Vaccine Immunology , Volume 19 (12): 1907 – Dec 1, 2012

Abstract

Analysis of Immune Responses against a Wide Range of Mycobacterium tuberculosis Antigens in Patients with Active Pulmonary Tuberculosis Desta Kassa a , b , Leonie Ran b , Wudneh Geberemeskel a , Mekashaw Tebeje a , Amelewerk Alemu a , Alemayehu Selase c , Belete Tegbaru a , Kees L. M. C. Franken d , Annemieke H. Friggen d , Krista E. van Meijgaarden d , Tom H. M. Ottenhoff d , Dawit Wolday e , Tsehaynesh Messele a and Debbie van Baarle b a Infectious and Noninfectious Diseases Research Directorate, Ethiopian Health and Nutrition Research Institute (EHNRI), Addis Ababa, Ethiopia b Department of Internal Medicine and Infectious Diseases and Department of Immunology, University Medical Center Utrecht, Utrecht, The Netherlands c St Peter Specialized TB Hospital, Addis Ababa, Ethiopia d Department of Infectious Diseases, Leiden University Medical Center, Leiden, The Netherlands e Medical Biotech Laboratory, Addis Ababa, Ethiopia ABSTRACT Characterizing host immune responses to molecular targets of Mycobacterium tuberculosis is essential to develop effective immunodiagnostics and better vaccines. We investigated the immune response against a large series of M. tuberculosis antigens, including 5 classical and 64 nonclassical (39 DosR regulon-encoded, 4 resuscitation-promoting factor (RPF), and 21 reactivation-associated) antigens in active-pulmonary-tuberculosis (TB) patients. Whole blood from TB patients ( n = 34) was stimulated in vitro with M. tuberculosis antigens. Gamma interferon (IFN-γ) was measured after 7 days of stimulation, using an enzyme-linked immunosorbent assay (ELISA). The majority of the study participants responded to the classical M. tuberculosis antigens TB10.4 (84.8%), early secreted antigenic target-6 kDa (ESAT-6)/CFP-10 (70.6%), and purified protein derivative (PPD) (55.9%). However, only 26.5% and 24.2% responded to HSP65 and Ag85A/B, respectively. Of the 64 nonclassical antigens, 23 (33.3%) were immunogenic (IFN-γ levels, >62 pg/ml) and 8 were strong inducers of IFN-γ (IFN-γ levels, ≥100 pg/ml). The RPF antigens were the most immunogenic. In addition, we observed distinct cytokine expression profiles in response to several M. tuberculosis antigens by multiplex immunoassay. Tumor necrosis factor alpha (TNF-α), interleukin 10 (IL-10), and IL-6 were commonly detected at high levels after stimulation with 4/15 latency antigens (Rv0081, Rv2006, Rv2629, and Rv1733c) and were found especially in supernatants of the three strong IFN-γ inducers (Rv2629, Rv1009, and Rv2389c). IL-8, IL-6, and IL-17 were exclusively detected after stimulation with Rv0574c, Rv2630, Rv1998, Rv054c, and Rv2028c. In conclusion, in active-pulmonary-TB patients, we identified 23 new immunogenic M. tuberculosis antigens. The distinct expression levels of IFN-γ, TNF-α, IL-6, and IL-10 in response to specific subsets of M. tuberculosis antigens may be promising for the development of immunodiagnostics.

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Publisher
American Society For Microbiology
Copyright
Copyright © 2012 by the American society for Microbiology.
ISSN
1556-6811
eISSN
1556-679X
DOI
10.1128/CVI.00482-12
pmid
23015647
Publisher site
See Article on Publisher Site

Abstract

Analysis of Immune Responses against a Wide Range of Mycobacterium tuberculosis Antigens in Patients with Active Pulmonary Tuberculosis Desta Kassa a , b , Leonie Ran b , Wudneh Geberemeskel a , Mekashaw Tebeje a , Amelewerk Alemu a , Alemayehu Selase c , Belete Tegbaru a , Kees L. M. C. Franken d , Annemieke H. Friggen d , Krista E. van Meijgaarden d , Tom H. M. Ottenhoff d , Dawit Wolday e , Tsehaynesh Messele a and Debbie van Baarle b a Infectious and Noninfectious Diseases Research Directorate, Ethiopian Health and Nutrition Research Institute (EHNRI), Addis Ababa, Ethiopia b Department of Internal Medicine and Infectious Diseases and Department of Immunology, University Medical Center Utrecht, Utrecht, The Netherlands c St Peter Specialized TB Hospital, Addis Ababa, Ethiopia d Department of Infectious Diseases, Leiden University Medical Center, Leiden, The Netherlands e Medical Biotech Laboratory, Addis Ababa, Ethiopia ABSTRACT Characterizing host immune responses to molecular targets of Mycobacterium tuberculosis is essential to develop effective immunodiagnostics and better vaccines. We investigated the immune response against a large series of M. tuberculosis antigens, including 5 classical and 64 nonclassical (39 DosR regulon-encoded, 4 resuscitation-promoting factor (RPF), and 21 reactivation-associated) antigens in active-pulmonary-tuberculosis (TB) patients. Whole blood from TB patients ( n = 34) was stimulated in vitro with M. tuberculosis antigens. Gamma interferon (IFN-γ) was measured after 7 days of stimulation, using an enzyme-linked immunosorbent assay (ELISA). The majority of the study participants responded to the classical M. tuberculosis antigens TB10.4 (84.8%), early secreted antigenic target-6 kDa (ESAT-6)/CFP-10 (70.6%), and purified protein derivative (PPD) (55.9%). However, only 26.5% and 24.2% responded to HSP65 and Ag85A/B, respectively. Of the 64 nonclassical antigens, 23 (33.3%) were immunogenic (IFN-γ levels, >62 pg/ml) and 8 were strong inducers of IFN-γ (IFN-γ levels, ≥100 pg/ml). The RPF antigens were the most immunogenic. In addition, we observed distinct cytokine expression profiles in response to several M. tuberculosis antigens by multiplex immunoassay. Tumor necrosis factor alpha (TNF-α), interleukin 10 (IL-10), and IL-6 were commonly detected at high levels after stimulation with 4/15 latency antigens (Rv0081, Rv2006, Rv2629, and Rv1733c) and were found especially in supernatants of the three strong IFN-γ inducers (Rv2629, Rv1009, and Rv2389c). IL-8, IL-6, and IL-17 were exclusively detected after stimulation with Rv0574c, Rv2630, Rv1998, Rv054c, and Rv2028c. In conclusion, in active-pulmonary-TB patients, we identified 23 new immunogenic M. tuberculosis antigens. The distinct expression levels of IFN-γ, TNF-α, IL-6, and IL-10 in response to specific subsets of M. tuberculosis antigens may be promising for the development of immunodiagnostics.

Journal

Clinical and Vaccine ImmunologyAmerican Society For Microbiology

Published: Dec 1, 2012

References