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Banerjee, S. and Ashok, N. and Raviprasad, P. and Katoch, V.M. and Murthy, K.J.R. and Hasnain, S.E. (2004) Mycobacterium tuberculosis (Mtb) isocitrate dehydrogenases show strong B cell response and distinguish vaccinated controls from TB patients. Proceedings of the National Academy of Sciences, 101 (34). pp. 12652-12657. ISSN 0027-8424

PNAS 101 p12652.pdf

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Proteins released from Mycobacterium tuberculosis (Mtb) during late logarithmic growth phase are often considered candidate components of immunogenic or autolysis markers. One such protein is isocitrate dehydrogenase (ICD), a key regulatory enzyme in the citric acid cycle. We have evaluated the immunogenic properties of two isoforms of Mtb ICD and compared them with the control antigens heat-shock protein 60 and purified protein derivative (PPD). PPD lacks the sensitivity to distinguish between bacillus Calmette-Guérin (BCG)-vaccinated and tuberculosis (TB)-infected populations, and, therefore, epidemiological relevance of PPD in BCG-vaccinated regions is debatable. We show that Mtb ICDs elicit a strong B cell response in TB-infected populations and can differentiate between healthy BCG-vaccinated populations and those with TB. The study population (n = 215) was categorized into different groups, namely, patients with fresh infection (n = 42), relapsed TB cases (n = 32), patients with extrapulmonary TB (n = 35), clinically healthy donors (n = 44), nontuberculous mycobacteria patients (n = 30), and non-TB patients (culture negative for acid-fast bacteria but carrying other infections, n = 32). The Mtb ICDs showed statistically significant antigenic distinction between healthy BCG-vaccinated controls and TB patients (P < 0.0001) and those with other infections. Although extrapulmonary infections could not be discriminated from healthy controls by heat-shock protein 60 (P = 0.2177), interestingly, the Mtb ICDs could significantly (P < 0.0001) do so. Our results highlight the immunodominant, immunosensitive, and immunospecific nature of Mtb ICDs and point to an unusual property of this tricarboxylic acid energy cycle enzyme.

Item Type: Article
Depositing User: Dr P Divakar
Date Deposited: 14 Oct 2015 09:21
Last Modified: 16 Dec 2015 07:04
URI: http://cdfd.sciencecentral.in/id/eprint/548

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