Proteins that are released from Mycobacterium tuberculosis during late logarithmic growth phase are often considered as 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 the two isoforms of M. tuberculosis ICDs and compared the same with the control antigen -HSP 60 as well as purified protein derivative (PPD). PPD lacks the sensitivity to distinguish between BCG vaccinated and TB-infected populations and therefore epidemiological relevance of PPD in BCG vaccinated regions is debatable. We show that M.tb ICDs elicit a strong B-cell response in TB- infected population and can differentiate between healthy-BCG vaccinated population and those with tuberculosis. The study population (n=215) was categorized into different groups, namely, patients with fresh infection (n=42), relapsed TB cases (n=32), patients with extra- pulmonary tuberculosis (n=35), clinically healthy donors (n=44), NTMs (n=30) and non-TB patients (culture negative for acid fast bacteria but carrying other infections, n=32). The M.tb ICDs showed statistically significant antigenic distinction between healthy-BCG vaccillated controls and tuberculosis patients (pO.OOOl) and those with other infections. While extrapulmonary infections could not be discriminated from healthy controls by HSP 60 (p= 0.2177) interestingly the M.tb ICDs could significantly (p 0.0001) do so. Our results highlight the immunodominant, immunosensitive and immunospecific nature of M. tb ICDs and point to a novel and an unusual property of this TCA cycle enzyme.
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