Specific Mycobacterium tuberculosis T cell responses to RD1-selected peptides for the monitoring of anti-tuberculosis therapy.

BACKGROUND: Recently, a selection of HLA class II-restricted epitopes of ESAT-6 and CFP-10 Mycobacterium tuberculosis proteins from the region of difference (RD) 1 have been described. We have evaluated the host interferon-gamma (IFN-γ) T cell response to these RD1 selected peptides at the beginning and during anti-tuberculosis therapy. METHODS: We studied 29 pulmonary TB patients enrolled at the beginning of treatment and 24 enrolled during treatment. We performed T-SPOT.TB and ELISPOT with RD1 selected peptides. RESULTS: Patients included at the beginning of treatment responded producing IFN-γ after antigen stimulation in 89.7% by means of T-SPOT.TB and 79.3% by means of RD1 selected ELISPOT. In contrast, for patients included during treatment the percentages were 87.5% and 25%, respectively. Differences in sensitivities between patients evaluated at the beginning and during treatment were only significant for RD1 selected ELISPOT (p < 0.0001). CONCLUSIONS: The host immune response to RD1 selected peptides is lower than to T-SPOT.TB during therapy. Immunological assays based on RD1 selected peptides may be useful tools for studying the immune response during anti-tuberculosis therapy.

IFN-gamma-release assays to diagnose TB infection in the immunocompromised individual.

The tuberculin skin test (TST) is used for diagnosing latent TB infection (LTBI). The main limitation of TST is its low sensitivity in populations with the highest risk of progression to active TB: immunosuppressed patients and young children. New IFN-gamma-based tests appear as an alternative to the TST. IFN-gamma-based tests seem more specific than the TST, being closely associated with LTBI factors, and not being affected by bacillus Calmette-Guérin vaccination. Indeterminate results are mainly related to immunosuppression. Looking at the available data, it seems prudent to recommend the utilization of IFN-gamma-based tests after a negative TST result, in order to increase the sensitivity of detecting LTBI cases in severely immunosuppressed patients. In summary, IFN-gamma-based tests appear to be a valuable tool, in combination with the TST, for diagnosing TB infection in immunosuppressed patients.

Quantitative evaluation of T-cell response after specific antigen stimulation in active and latent tuberculosis infection in adults and children.

We have evaluated the quantitative T-cell response after specific Mycobacterium tuberculosis antigen stimulation in active tuberculosis (TB) and latent TB infection (LTBI) patients. In adults, the median number of T cells after RD1 antigen stimulation was significantly higher in active TB patients than in LTBI patients. In children, the number of responder T cells against the specific antigens was higher in active TB than in LTBI patients, although the differences were not significant. In summary, in patients with suspected clinical TB, although there is overlapping in the number of responder T cells between both groups, a T-cell count above the described threshold could suggest active TB, especially in patients with a high probability of having active TB and low probability of having LTBI. In addition, the results are consistent with the current evidence that T-cell response may indicate mycobacterial burden and disease activity.

T-cell responses to the Mycobacterium tuberculosis-specific antigens in active tuberculosis patients at the beginning, during, and after antituberculosis treatment.

The objectives of the study were to assess the performance of the QuantiFERON-TB Gold In-Tube (QFN-G-IT) and the T-SPOT.TB tests in the immunodiagnosis of active tuberculosis (TB) in adult patients, and to study the T-cell interferon gamma (IFN-gamma) responses during treatment and in patients who have recovered after curative treatment and self-healed TB patients. When only analyzing patients included at the beginning of treatment, the sensitivity was 83.3% for T-SPOT.TB and 69.4% for QFN-G-IT. In contrast, when evaluating patients during treatment, the sensitivity of the T-SPOT.TB and QFN-G-IT decreased to 69.8% and 48.8%, respectively. The response to the specific antigens increased after finishing the treatment compared with the values during the treatment. The T-SPOT.TB was more sensitive in diagnosing active TB than the QFN-G-IT. The IFN-gamma tests could be used as a complementary method in the diagnosis of active TB.

Comparison of two commercially available gamma interferon blood tests for immunodiagnosis of tuberculosis.

We evaluated the T-SPOT.TB and Quantiferon-TB Gold In tube (QFN-G-IT) tests for diagnosing Mycobacterium tuberculosis infection. T-SPOT.TB was more sensitive than QFN-G-IT in diagnosing both active and latent infection. Both gamma interferon tests were unaffected by prior Mycobacterium bovis BCG vaccination. Among children who were not BCG vaccinated but had a positive tuberculin skin test, QFN-G-IT was negative in 53.3% of cases, and T-SPOT.TB was negative in 50% of cases.