Study of CD27 and CCR4 Markers on Specific CD4+ T-Cells as Immune Tools for Active and Latent Tuberculosis Management.

The immunological characterization of different cell markers has opened the possibility of considering them as immune tools for tuberculosis (TB) management, as they could correlate with TB latency/disease status and outcome. CD4+ T-cells producing IFN-γ+ with a low expression of CD27 have been described as an active TB marker. In addition, there are unknown homing receptors related to TB, such as CCR4, which might be useful for understanding TB pathogenesis. The aim of our study is focused on the assessment of several T-cell subsets to understand immune-mechanisms in TB. This phenotypic immune characterization is based on the study of the specific immune responses of T-cells expressing CD27 and/or CCR4 homing markers. Subjects enrolled in the study were: (i) 22 adult patients with active TB, and (ii) 26 individuals with latent TB infection (LTBI). Blood samples were drawn from each patient. The expression of CD27 and/or CCR4 markers were analyzed within CD4+ T-cells producing: (i) IFN-γ+, (ii) TNF-α+, (iii) TNF-α+IFN-γ+, and (iv) IFN-γ+ and/or TNF-α+. The percentage of CD27- within all CD4+ T-cell populations analyzed was significantly higher on active TB compared to LTBI after PPD or ESAT-6/CFP-10 stimulation. As previously reported, a ratio based on the CD27 median fluorescence intensity (MFI) was also explored (MFI of CD27 in CD4+ T-cells over MFI of CD27 in IFN-γ+CD4+ T-cells), being significantly increased during disease (p < 0.0001 after PPD or ESAT-6/CFP-10 stimulation). This ratio was also assessed on the other CD4+ T-cells functional profiles after specific stimulation, being significantly associated with active TB. Highest diagnostic accuracies for active TB (AUC ≥ 0.91) were achieved for: (i) CD27 within IFN-γ+TNF-α+CD4+ T-cells in response to ESAT-6/CFP-10, (ii) CD27 and CCR4 markers together within IFN-γ+CD4+ T-cells in response to PPD, and (iii) CD27 MFI ratio performed on IFN-γ+TNF-α+CD4+ T-cells after ESAT-6/CFP-10 stimulation. The lowest diagnostic accuracy was observed when CCR4 marker was evaluated alone (AUC ≤ 0.77). CD27 and CCR4 expression detection could serve as a good method for immunodiagnosis. Moreover, the immunological characterization of markers/subset populations could be a promising tool for understanding the biological basis of the disease.

Varenicline in smokers with severe or very severe COPD after 24 weeks of treatment. A descriptive analysis: VALUE study.

A large number of COPD patients are smokers. The particular characteristics of this group as well as their need to quit usually require psychological counselling and pharmacological treatment to achieve abstinence and, often, intensively. Little information is available about this issue.  The main objective of the study was to evaluate the effectiveness of varenicline after 24 weeks of treatment, with continuous abstinence between weeks 9 and 24.  This study was a post-authorization, open label, observational study of prospective follow-up. Patients included were smokers with severe or very severe COPD criteria who were treated with varenicline for 24 weeks, i.e. with a 12-week extension over the usual treatment.  The outcomes in the population of subjects completing 24 weeks of follow-up were at week 24: continuous abstinence 36.8%, 7 days point prevalence abstinence 65.7%, and continuous smoking 31.5%.The outcomes in the intention-to-treat population included at baseline were: continuous abstinence 17.7% of patients, 7 days point prevalence abstinence 31.6%, continuous smoking 15.1% and not valid/unknown 51.8%.  The mean CAT score at week 24 was 15 and reduction from the baseline was 3.77 (paired T test, p<0.01). The most common adverse events reported were nausea, vivid dreams, stomach ache, insomnia, headache and vomiting.  Patients included in VALUE were active smokers despite all of them had a severe COPD which suggests a very high degree of dependence. Although the study do not allow to infer the results to the global population of smokers with severe COPD, the outcomes have shown that, at 24 weeks follow up 36.8% of the patients were successful in quitting but from 79 patients enrolled initially only 17.7% quit.