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

Content Provider	PubMed Central
Author	Kassa, Desta Ran, Leonie Wudneh, Geberemeskel Tebeje, Mekashaw Alemu, Amelewerk Alemayehu, Selase Belete, Tegbaru Franken, Kees L. M. C. Friggen, Annemieke H. Van, Meijgaarden Krista E. Ottenhoff, Tom H. M. Wolday, Dawit Messele, Tsehaynesh Baarle, Debbie Van
Copyright Year	2012
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.
Related Links	http://dx.doi.org/10.1128/cvi.00482-12
Ending Page	1915
Page Count	9
Starting Page	1907
File Format	PDF
ISSN	15566811
e-ISSN	1556679X
Journal	Clinical and Vaccine Immunology : CVI
Issue Number	12
Volume Number	19
Language	English
Publisher	American Society for Microbiology
Publisher Date	2012-12-01
Access Restriction	Open
Rights Holder	American Society for Microbiology
Subject Keyword	Immunology Immunology and Allergy Microbiology (medical) Clinical Biochemistry Research in Higher Education
Content Type	Text
Resource Type	Article
Subject	Immunology and Allergy Clinical Biochemistry Immunology Microbiology (medical)

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