Non-tuberculous mycobacterial pulmonary disease: an Italian National survey.

The incidence of non-tuberculous mycobacteria (NTM) infection is increasing in Europe. However, a picture of Italian epidemiology and clinical practice is missing. We performed a national Italian survey involving 42 respiratory medicine departments. The NTM species more frequently isolated were Mycobacterium avium complex, followed by M. xenopi and M. kansasii. Patients with NTM were more frequently female (57%), and over 60 years of age, with bronchiectasis and COPD as main comorbidities. Bronchoscopic samples were widely used in the diagnostic phase. Of all patients with NTM, 73% met the criteria for NTM pulmonary disease. Despite strong adherence to the guidelines, physicians found significant difficulties related to pharmacological adverse events, patients' compliance and poor outcomes. (Sarcoidosis Vasc Diffuse Lung Dis 2018; 35: 21-25).

The role of interferon-gamma release assays in predicting the emergence of active tuberculosis in the setting of biological treatment: a case report and review of the literature.

Conversions and reversions of interferon-gamma (IFN-γ) release assays (IGRAs) were observed when these tests were repeated over time in the same individuals, including those treated with biological agents. In most studies, the variability of IFN-γ plasma levels was not paralleled by clinical change, but a few exceptions exist, in which IGRA conversion predicted the emergence of active tuberculosis (TB). We report the case of a Peruvian patient with rheumatoid arthritis (RA) and Crohn's disease scheduled for treatment with adalimumab. TB screening demonstrated latent TB infection (LTBI), and the patient was started on isoniazid (INH) for 9 months. Adalimumab was initiated after 1 month since INH. QuantiFERON-TB Gold In-Tube, one of the IGRAs currently available, was serially repeated to monitor the status of TB infection during treatment with the biological agent. The patient developed active TB preceded by progressively rising levels of released IFN-γ. We came to know that she had withdrawn INH after 2 months on her own initiative. Considering the low rate of INH completion, serial IGRAs may help in the clinical vigilance during prophylaxis as well as anti-TNF treatment, at least in patients presenting other risk factors aside from the state of immunosuppression.

An abnormal phenotype of lung Vγ9Vδ2 T cells impairs their responsiveness in tuberculosis patients.

Antigen-specific γδ T cells represent an early innate defense known to play an important role in anti-mycobacterial immunity. We have investigated the immune functions of Vγ9Vδ2 T cells from Broncho-Alveolar lavages (BAC) samples of active TB patients. We observed that BAC Vγ9Vδ2 T cells presented a strong down-modulation of CD3 expression compared with Vγ9Vδ2 T cells from peripheral blood. Furthermore, Vγ9Vδ2 T cells mainly showed a central memory phenotype, expressed high levels of NK inhibitory receptors and TEMRA cells showed low expression of CD16 compared to circulating Vγ9Vδ2 T cells. Interestingly, the ability of BAC Vγ9Vδ2 T cells to respond to antigen stimulation was dramatically reduced, differently from blood counterpart. These observations indicate that γδ T cell functions are specifically impaired in situ by active TB, suggesting that the alveolar ambient during tuberculosis may affect resident γδ T cells in comparison to circulating cells.

Design of immunogenic peptides from Mycobacterium tuberculosis genes expressed during macrophage infection.

In vitro diagnosis of MTB-infection uses MTB-proteins coded for by genes of the region of differentiation 1 (RD1) of the MTB genome. This study wants to test if proteins preferentially expressed during MTB-intracellular growth might provide new targets for the diagnosis of MTB-infection. To this end seventy-five multiepitopic HLA-promiscuous MTB-peptides were designed by quantitative implemented peptide-binding motif analysis from 3 MTB-protein genes expressed in activated human macrophages (MA), 4 genes expressed during growth in non-activated human macrophages (MN-A), 12 housekeeping genes (HKG) and 6 genes of the RD1 region (RD1) as control. ELISpot for IFN-was performed to measure the responses of PBMCs deriving from 45 patients affected by active tuberculosis and 34 controls. In active-TB patients, the mean response to RD1-derived peptides was higher than that to either MA (p<0.01), MN-A (p<0.008) or HKG (p<0.01) derived peptides. In TST-positive subjects all selected peptides elicited significant IFN-T-cell responses (p<0.02 compared to TST-negatives), but without differences between the subgroups. Further, T-cell responses to RD1 peptides were lower in the 23 active-TB treated patients than in the untreated ones (p<0.01). The response to MA peptides in treated active-TB was higher than when untreated (p<0.01). These results demonstrate that the use of in vitro models of MTB-intracellular infection to select MTB gene products for further in silico and in vitro assessment of their immunogenicity have the potential to identify novel antigens amenable to the design of new tools for diagnosis and monitoring of tuberculosis.