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.