HIV-infected patients developing tuberculosis disease show early changes in the immune response to novel Mycobacterium tuberculosis antigens. frontiers in Immunology
Meier et al. performed a case-control study to evaluate the utility of novel M. tuberculosis antigens for early diagnosis of tuberculosis (TB) in people with HIV.
Authors included patients in the Swiss HIV Cohort Study who developed TB and matched controls without TB. In these individuals, stored lymphocytes were stimulated with 10 novel M. tuberculosis antigens at four time points prior to TB diagnosis and differences in cytokine responses between cases and controls assessed.
The study included 4 individuals who developed pulmonary TB, 4 who experienced extrapulmonary TB, one who received a diagnosis of both pulmonary and extrapulmonary disease, and 9 controls without TB. Median cytokine concentrations induced by 3 out of the 10 novel M. tuberculosis antigens were significantly higher in the TB cases compared with controls in the latest time point prior to TB diagnosis (at a median of 117 days prior to TB diagnosis, IQR 29-312). Cytokine levels induced by one of the novel antigens were significantly higher in cases compared to controls even at time point three, which was at a median of 440 days prior to TB diagnosis (IQR 68-846). Traditional interferon-gamma release assays did not discriminate cases from controls at any time point.
In summary, the present study showed that cytokine responses induced by novel M. tuberculosis antigens of patients with and without TB differed already more than 12 months prior to TB diagnosis, and for one cytokine already between 1 and 2 years prior to TB diagnosis. These findings underline that dividing TB disease into latent or active is an inadequate representation of the full spectrum of disease, and the results may provide new possibilities for early detection of TB disease in people with HIV.