Immunogenicity of 60 novel latency-related antigens of Mycobacterium tuberculosis

The aim of our work here was to evaluate the immunogenicity of 60 mycobacterial antigens, some of which have not been previously assessed, notably a novel series of in vivo -expressed Mycobacterium tuberculosis (IVE-TB) antigens. We enrolled 505 subjects and separated them in individuals with and without latent tuberculosis infection (LTBI) vs. patients with active tuberculosis (TB). Following an overnight and 7 days stimulation of whole blood with purified recombinant M. tuberculosis antigens, interferon-γ (IFN-γ) levels were determined by ELISA. Several antigens could statistically significantly differentiate the groups of individuals. We obtained promising antigens from all studied antigen groups [dormancy survival regulon (DosR regulon) encoded antigens; resuscitation-promoting factors (Rpf) antigens; IVE-TB antigens; reactivation associated antigens]. Rv1733, which is a probable conserved transmembrane protein encoded in DosR regulon, turned out to be very immunogenic and able to discriminate between the three defined TB status, thus considered a candidate biomarker. Rv2389 and Rv2435n, belonging to Rpf family and IVE-TB group of antigens, respectively, also stood out as LTBI biomarkers. Although more studies are needed to support our findings, the combined use of these antigens would be an interesting approach to TB immunodiagnosis candidates

Assessment of the influence of direct tobacco smoke on infection and active TB management

Smoking is a risk factor for tuberculosis (TB) infection and disease progression. Tobacco smoking increases susceptibility to TB in a variety of ways, one of which is due to a reduction of the IFN-γ response. Consequently, an impaired immune response could affect performance of IFN-γ Release Assays (IGRAs).Miguel Servet program of the Instituto de Salud Carlos III (Spain). ML was supported by a joint ERS/SEPAR fellowship (LTRF 2015). The research was partially supported by a grant from the Instituto de Salud Carlos III (PI 13/01546 and PI 16/01912), integrated in the Plan Nacional de I+D+I and cofunded by the ISCIII Subdirección General de Evaluación and the Fondo Europeo de Desarrollo Regional (FEDER); and a grant from the Sociedad Española de Neumología y Cirugía Torácica (SEPAR; Barcelona, Spain) (Smoking Integrated Research Programme Call) to NA

Búsqueda activa de tuberculosis en inmigrantes en Barcelona

Objetivo: Conocer la prevalencia de la infección y de la enfermedad tuberculosa en inmigrantes económicos y recientes en Barcelona. Sujetos y método: Reconocimiento médico de inmigrantes. Se practicó la prueba de tuberculina (PT) y se indagó la presencia de cicatriz posvacunación antituberculosa. Se estableció el dintel de positividad de la PT en 5 mm para los no vacunados y en 15 mm para los vacunados. Resultados: Se examinó a 3.651 personas, pero sólo se incluyó en el análisis a las 3.151 que completaron el estudio. Se diagnosticó a 18 enfermos (tasa de 571,2 por 100.000) y el 50,6% se catalogó como reactores positivos a la PT, siendo el 34,4% reactores por infección y 16,3% por posible vacunación antituberculosa. El porcentaje de reactores es estadísticamente superior al encontrado en una población autóctona. La edad, ser varón, la región de procedencia, la mayor pobreza y la mayor tasa de enfermedad en el país de origen se mostraron asociados a la prevalencia de la infección tuberculosa de los inmigrantes. Discusión: La búsqueda activa se ha mostrado eficiente. La interferencia de la vacunación antituberculosa modifica mucho los resultados, según el dintel de positividad de la PT que se establezca. Se recomienda realizar la PT junto con la radiología del tórax. La inmigración modificará la endemia tuberculosa del país y se han de diseñar estrategias específicas para afrontar este nuevo reto de la tuberculosi

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

Tobacco Smoking and Second-Hand Smoke Exposure Impact on Tuberculosis in Children

Little is known about whether second-hand smoke (SHS) exposure affects tuberculosis (TB). Here, we investigate the association of cigarette smoke exposure with active TB and latent TB infection (LTBI) in children, analyzing Interferon-Gamma Release Assays' (IGRAs) performance and cytokine immune responses. A total of 616 children from contact-tracing studies were included and classified regarding their smoking habits [unexposed, SHS, or smokers]. Risk factors for positive IGRAs, LTBI, and active TB were defined. GM-CSF, IFN-γ, IL-2, IL-5, IL-10, IL-13, IL-22, IL-17, TNF-α, IL-1RA and IP-10 cytokines were detected in a subgroup of patients. Being SHS exposed was associated with a positive IGRA [aOR (95% CI): 8.7 (5.9-12.8)] and was a main factor related with LTBI [aOR (95% CI): 7.57 (4.79-11.94)] and active TB [aOR (95% CI): 3.40 (1.45-7.98)]. Moreover, IGRAs' sensitivity was reduced in active TB patients exposed to tobacco. IL-22, GM-CSF, IL-5, TNF-α, IP-10, and IL-13 were less secreted in LTBI children exposed to SHS. In conclusion, SHS is associated with LTBI and active TB in children. In addition, false-negative IGRAs obtained on active TB patients exposed to SHS, together with the decrease of specific cytokines released, suggest that tobacco may alter the immune response.This research was supported by: (i) a grant from the Instituto de Salud Carlos III (PI13/01546, PI16/01912, and PI18/00411), integrated in the Plan Nacional I+D+I and co-funded by the ISCIII Subdirección General de Evaluación and the Fondo Europeo de Desarrollo Regional (FEDER) and CERCA Programme/Generalitat de Catalunya; and (ii) a grant from the Sociedad Española de Neumología y Cirugía Torácica (SEPAR; Barcelona, Spain) (Smoking Integrated Research Programme Call

Assessment of the influence of direct tobacco smoke on infection and active TB management

Smoking is a risk factor for tuberculosis (TB) infection and disease progression. Tobacco smoking increases susceptibility to TB in a variety of ways, one of which is due to a reduction of the IFN-γ response. Consequently, an impaired immune response could affect performance of IFN-γ Release Assays (IGRAs)

X-chromosome tiling path array detection of copy number variants in patients with chromosome X-linked mental retardation

Background: Aproximately 5–10% of cases of mental retardation in males are due to copy number variations (CNV) on the X chromosome. Novel technologies, such as array comparative genomic hybridization (aCGH), may help to uncover cryptic rearrangements in X-linked mental retardation (XLMR) patients. We have constructed an X-chromosome tiling path array using bacterial artificial chromosomes (BACs) and validated it using samples with cytogenetically defined copy number changes. We have studied 54 patients with idiopathic mental retardation and 20 controls subjects. Results: Known genomic aberrations were reliably detected on the array and eight novel submicroscopic imbalances, likely causative for the mental retardation (MR) phenotype, were detected. Putatively pathogenic rearrangements included three deletions and five duplications (ranging between 82 kb to one Mb), all but two affecting genes previously known to be responsible for XLMR. Additionally, we describe different CNV regions with significant different frequencies in XLMR and control subjects (44% vs. 20%). Conclusion:/nThis tiling path array of the human X chromosome has proven successful for the detection and characterization of known rearrangements and novel CNVs in XLMR patients

Assessment of the influence of direct tobacco smoke on infection and active TB management

Background. Smoking is a risk factor for tuberculosis (TB) infection and disease progression. Tobacco smoking increases susceptibility to TB in a variety of ways, one of which is due to a reduction of the IFN-γ response. Consequently, an impaired immune response could affect performance of IFN-γ Release Assays (IGRAs). Objective. In the present study, we assess the impact of direct tobacco smoking on radiological manifestations, sputum conversion and immune response to Mycobacterium tuberculosis, analyzing IFN-γ secretion by IGRAs. Methods. A total of 525 participants were studied: (i) 175 active pulmonary TB patients and (ii) 350 individuals coming from contact tracing studies, 41 of whom were secondary TB cases. Clinical, radiological and microbiological data were collected. T-SPOT.TB and QFN-G-IT were processed according manufacturer's instructions. Results. In smoking patients with active TB, QFN-G-IT (34.4%) and T-SPOT.TB (19.5%) had high frequencies of negative results. In addition, by means of an unconditional logistic regression,smoking was a main factor associated with IGRAs' false-negative results (aOR: 3.35; 95% CI:1.47±7.61; p<0.05). Smoking patients with active TB presented a high probability of having cavitary lesions (aOR: 1.88; 95%CI:1.02±3.46;p<0.05). Mean culture negativization (months) ± standard deviation (SD) was higher in smokers than in non-smokers (2.47±1.3 versus 1.69±1.4). Latent TB infection (LTBI) was favored in smoking contacts, being a risk factor associated with infection (aOR: 11.57; 95%CI:5.97±22.41; p<0.00005). The IFN-γ response was significantly higher in non-smokers than in smokers. Smoking quantity and IFN-γ response analyzed by IGRAs were dose-dependent related. Conclusions. Smoking had a negative effect on radiological manifestations, delaying time of sputum conversion. Our data establish a link between tobacco smoking and TB due to a weakened IFN- γ response caused by direct tobacco smoke