Frontiers in Cellular and Infection Microbiology, 2022
Alterations of myeloid cell populations have been reported in patients with tuberculosis (TB). In... more Alterations of myeloid cell populations have been reported in patients with tuberculosis (TB). In this work, we studied the relationship between myeloid-derived suppressor cells (MDSC) and monocytes subsets with the immunological responsiveness of TB patients. Individuals with active TB were classified as low responders (LR-TB) or high responders (HR-TB) according to their T cell responses against a cell lysate of Mycobacterium tuberculosis (Mtb-Ag). Thus, LR-TB, individuals with severe disease, display a weaker immune response to Mtb compare to HR-TB, subjects with strong immunity against the bacteria. We observed that LR-TB presented higher percentages of CD16 positive monocytes as compared to HR-TB and healthy donors. Moreover, monocyte-like (M-MDSC) and polymorphonuclear-like (PMN-MDSC) MDSC were increased in patients and the proportion of M-MDSC inversely correlated with IFN-γ levels released after Mtb-Ag stimulation in HR-TB. We also found that LR-TB displayed the highest perc...
El objetivo del presente estudio fue determinar el rédito diagnóstico y los factores asociados a ... more El objetivo del presente estudio fue determinar el rédito diagnóstico y los factores asociados a mayor morbimortalidad en la biopsia quirúrgica de pulmón en pacientes con enfermedad intersticial difusa. Se analizaron en forma retrospectiva los registros clínicos de 71 pacientes. Se registraron complicaciones en 16 pacientes (22.5%). La mortalidad operatoria fue 11.2%. Los pacientes en quienes la biopsia se realizó por videotoracoscopia (n = 52) y por toracotomía (n = 17) tuvieron la misma duración de estadía en terapia intensiva y de estadía hospitalaria. La tasa de complicaciones (22.2% vs. 21.0%, p = 1.0000) y la mortalidad (9.2 vs. 15.7%, p = 0.2738) no fueron diferentes. Ocho pacientes murieron dentro de los 30 días. La prevalencia de inmunosupresión (4/8 vs. 9/63, p = 0.0325) fue significativamente superior en el grupo de pacientes fallecidos. Estos pacientes tuvieron valores preoperatorios más elevados de urea (50 ± 20.1 mg/dl vs. 31.2 ± 10.3 mg/ dl, p = 0.0013) y menores valo...
El objetivo del estudio fue determinar las características clínicas de los pacientes con esclerod... more El objetivo del estudio fue determinar las características clínicas de los pacientes con esclerodermia y compromiso pulmonar y evaluar si existen factores clínicos predictores de mayor riesgo de enfermedad intersticial. Se estudiaron en forma retrospectiva 40 pacientes con esclerodermia. Fueron divididos en 2 grupos: capacidad de difusión del monóxido de carbono (DLCO) normal (n = 22) y DLCO disminuida (n = 18, 45%). Los pacientes con DLCO disminuida no fueron diferentes en edad (51.1 ± 13.5 vs. 53.5 ± 9.3 años, p = 0.5182), sexo (varones 13.6%, p = 0.6088 ), presencia de Raynaud (86.6% vs. 85%, p = 0.6272), síndrome de ojo seco (6.2% vs. 10.5%, p = 1.0000) prevalencia de enfermedad difusa (94.1% vs. 83.3%, p = 0.6026) o de dilatación esofágica. El tiempo de evolución de la enfermedad no fue diferente. La sensibilidad de la disnea para detectar una DLCO alterada fue 46.6% con una especificidad del 90% y la de la caída de la saturación de O2 (SaO2) del 71.4% y 80% respectivamente. Lo...
Prostaglandin E2 (PGE2), an active lipid compound derived from arachidonic acid, regulates differ... more Prostaglandin E2 (PGE2), an active lipid compound derived from arachidonic acid, regulates different stages of the immune response of the host during several pathologies such as chronic infections or cancer. Manipulation of PGE2 levels was proposed as an approach for countering the Type I IFN signature of tuberculosis (TB), but very limited information exists about this pathway in patients with active TB. Here, we demonstrated that PGE2 exerts a potent immunosuppressive action during the immune response of the human host against M. tuberculosis. Thus, we showed that PGE2 inhibited both lymphoproliferation and cytokine production of proinflammatory cytokines, together with a significant reduction of the surface expression of several immunological receptors in human cells. However, PGE2 promoted the autophagic flux of antigen-stimulated monocytes, even in the presence of IFNα. In this way, the attenuation of inflammation and immunopathology caused by an excessive immune response emerg...
Tuberculin skin test (TST) and IFN-γ release assays are currently used to detect Mycobacterium tu... more Tuberculin skin test (TST) and IFN-γ release assays are currently used to detect Mycobacterium tuberculosis (Mtb) infection but none of them differentiate active from latent infection (LTBI). Since improved tests to diagnose Mtb infection are required, we studied the immune response to Mtb latency antigen Rv2626c in individuals exposed to the bacteria during different periods. Tuberculosis patients (TB), TB close contacts (CC: subjects exposed to Mtb for less than three months) and healthcare workers (HW: individuals exposed to Mtb at least two years) were recruited and QuantiFERON (QFT) assay, TST and IFN-γ secretion to Rv2626c were analyzed. Twenty-two percent of the individuals assessed had discordant results between QFT and TST tests. Furthermore, QFT negative and QFT positive individuals produced differential levels of IFN-γ against Rv2626c, in direct association with their exposure period to Mtb. Actually, 91% of CC QFT negative subjects secreted low levels of IFN-γ to Rv2626c...
Dendritic cells (DCs) are a key player in the host response to the tuberculosis (TB) agent, Mycob... more Dendritic cells (DCs) are a key player in the host response to the tuberculosis (TB) agent, Mycobacterium tuberculosis (Mtb), which interfere with DC functions. However, how metabolic pathways influence DC function and activation in TB is unknown. We found that Mtb triggers both glycolysis and to a lesser extent mitochondrial respiration in human monocyte-derived DCs. This was accompanied by an increase in expression of the transcription factor HIF-1α and several glycolytic genes, dependent on TLR2 engagement by Mtb. Inhibition of either HIF-1α or glycolysis resulted in a strong alteration of the DCs migration capacities. In addition, DCs derived from monocytes of TB patients are deficient in inducing glycolysis and cell migration in response to Mtb, rescuable by induction of HIF-1α activity. Indeed, monocytes from TB patients are already highly glycolytic, differentiating into poorly migratory DCs. The data uncover a crucial role for glycolysis in DC migration and suggest that its ...
ABSTRACT Neutrophils infected with Mycobacterium tuberculosis (Mtb) predominate in tuberculosis p... more ABSTRACT Neutrophils infected with Mycobacterium tuberculosis (Mtb) predominate in tuberculosis patients’ lungs. Neutrophils phagocytose the pathogen, but the mechanism of pathogen elimination is controversial. Macroautophagy/autophagy, a crucial mechanism for several neutrophil functions, can be modulated by immunological mediators. The costimulatory molecule SLAMF1 can act as a microbial sensor in macrophages being also able to interact with autophagy-related proteins. Here, we demonstrate for the first time that human neutrophils express SLAMF1 upon Mtb-stimulation. Furthermore, SLAMF1 was found colocalizing with LC3B+ vesicles, and activation of SLAMF1 increased neutrophil autophagy induced by Mtb. Finally, tuberculosis patients’ neutrophils displayed reduced levels of SLAMF1 and lower levels of autophagy against Mtb as compared to healthy controls. Altogether, these results indicate that SLAMF1 participates in neutrophil autophagy during active tuberculosis. Abbreviations: AFB: acid-fast bacilli; BafA1: bafilomycin A1; CLL: chronic lymphocytic leukemia; DPI: diphenyleneiodonium; EVs: extracellular vesicles; FBS: fetal bovine serum; HD: healthy donors; HR: high responder (tuberculosis patient); IFNG: interferon gamma; IL1B: interleukin 1 beta; IL17A: interleukin 17A; IL8: interleukin 8; LR: low responder (tuberculosis patient); mAb: monoclonal antibody; MAP1LC3/LC3: microtubule associated protein 1 light chain 3; MAPK: mitogen-activated protein kinase; MAPK1/ERK2: mitogen-activated protein kinase 1; MAPK14/p38: mitogen-activated protein kinase 14; Mtb: Mycobacterium tuberculosis; Mtb-Ag: Mycobacterium tuberculosis, Strain H37Rv, whole cell lysate; NETs: neutrophils extracellular traps; PPD: purified protein derivative; ROS: reactive oxygen species; PIK3C3/VPS34: phosphatidylinositol 3-kinase catalytic subunit type 3; SLAMF1: signaling lymphocytic activation molecule family member 1; TB: tuberculosis; TLR: toll like receptor
pacientes con iniciacion aguda la mortalidad fue significativamente mas elevada (36.3% vs. 7.1%, ... more pacientes con iniciacion aguda la mortalidad fue significativamente mas elevada (36.3% vs. 7.1%, p = 0.0223). La biopsia aporto un diagnostico especifico en 100% de los pacientes y cambio la estrategia terapeutica en 66.7%. En conclusion, la biopsia de pulmon por via toracoscopica es un procedimiento util y seguro en los pacien- tes con enfermedad intersticial difusa del pulmon. Sin embargo, en el grupo de pacientes inmunocomprometidos, con cuadros de presentacion aguda y con insuficiencia respiratoria preoperatoria, la mortalidad es elevada y de- ben balancearse muy criticamente los riesgos contra los beneficios en ese grupo de enfermos. Palabras clave: biopsia de pulmon, biopsia toracoscopica, enfermedad intersticial pulmonar, neumonia intersticial usual Abstract Lung biopsy for the diagnosis of interstitial lung disease. The objective of this study was to determine the morbidity, mortality and diagnostic yield of video assisted thoracoscopy (VATS) and thoracotomy lung biopsy in i...
The objective of this study was to determine clinical predictors of interstitial lung disease in ... more The objective of this study was to determine clinical predictors of interstitial lung disease in patients with systemic sclerosis (SSc) and pulmonary involvement as defined by presence of a decreased diffusing capacity for carbon monoxide (DLCO). Forty subjects with SSc were retrospectively evaluated. Patients were categorized according to their level of DLCO (< o > or = 80% of predicted). Sensitivity of dyspnea to detect a decreased DLCO was 46.6% and specificity 90%, whereas oxygen desaturation showed a sensitivity of 71.4% and a specificity of 80%. Patients with decreased DLCO (n = 18) were not different in age (51.1 +/- 13.5 vs. 53.5 +/- 9.3 y, p = 0.5182), sex (male 13.6%, p = 0.6088), prevalence of Raynaud (86.6% vs. 85%, p = 0.6272), sicca syndrome (6.2% vs. 10.5% p = 1.0000) diffuse cutaneous involvement (94.1% vs. 83.3%, p = 0.6026) or esophageal dilatation. The duration of symptoms since diagnosis was no different. Prevalence of pulmonary hypertension assessed by Dop...
Lung involvement in systemic sclerosis. The objective of this study was to determine clinical pre... more Lung involvement in systemic sclerosis. The objective of this study was to determine clinical predictors of interstitial lung disease in patients with systemic sclerosis (SSc) and pulmonary involvement as defined by presence of a decreased diffusing capacity for carbon monoxide (DLCO). Forty subjects with SSc were retrospectively evaluated. Patients were categorized according to their level of DLCO (< o ≥ 80% of predicted). Sensitivity of dyspnea to detect a decreased DLCO was 46.6% and specificity 90%, whereas oxygen desaturation showed a sensitivity of 71.4% and a specificity of 80%. Patients with decreased DLCO (n = 18) were not different in age (51.1 ± 13.5 vs. 53.5 ± 9.3 y, p = 0.5182), sex (male 13.6%, p = 0.6088), prevalence of Raynaud (86.6% vs. 85%, p = 0.6272), sicca syndrome (6.2% vs. 10.5% p = 1.0000) diffuse cutaneous involvement (94.1% vs. 83.3%, p = 0.6026) or esophageal dilatation. The duration of symptoms since diagnosis was no different. Prevalence of pulmonary ...
Prostaglandin E2 (PGE2), an active lipid compound derived from arachidonic acid, regulates differ... more Prostaglandin E2 (PGE2), an active lipid compound derived from arachidonic acid, regulates different stages of the immune response of the host during several pathologies such as chronic infections or cancer. In fact, manipulation of PGE2 levels was proposed as an approach for countering the Type I IFN signature of tuberculosis (TB). However, very limited information regarding the PGE2 pathway in patients with active TB is currently available. In the present work, we demonstrated that PGE2 exerts a potent immunosuppressive action during the immune response of the human host against Mycobacterium tuberculosis (Mtb) infection. Actually, we showed that PGE2 significantly reduced lymphoproliferation, the production of proinflammatory cytokines, and the surface expression of several immunological receptors. On the other hand, PGE2 promoted autophagy in monocytes and neutrophils cultured with Mtb antigens. These results suggest that PGE2 might be attenuating the excessive inflammatory immu...
The objective of this study was to determine the morbidity, mortality and diagnostic yield of vid... more The objective of this study was to determine the morbidity, mortality and diagnostic yield of video assisted thoracoscopy (VATS) and thoracotomy lung biopsy in interstitial lung disease (ILD). Clinical records of 71 patients were retrospectively analyzed. There was no difference in mean hospital stay, intensive care unit stay and duration of chest tube drainage in patients with VATS (n = 52) compared with those undergoing open thoracotomy (n = 17). Complications rate (22.2% vs. 21.0%, p = 1.0000) and operating mortality (9.2 vs. 15.7%, p = 0.2738) were also similar. Overall, complications occurred in 16 patients (22.5%). Thirty-day mortality rate was 11.2% (n = 8). Prevalence of immunosupression (4/8 vs. 9/63, p = 0.0325) was significantly higher in the group of patients who died. No surviving patients had higher values of plasmatic urea (50 +/- 20.1 mg/dl vs. 31.2 +/- 10.3 mg/dl, p = 0.0013) or lower values of preoperative oxygen saturation (SaO2): 82.7 +/- 14.8% vs. 92.8 +/- 3.4%,...
Alterations of myeloid cell populations have been reported in patients with tuberculosis (TB). Si... more Alterations of myeloid cell populations have been reported in patients with tuberculosis (TB). Since myeloid-derived suppressor cells (MDSC) and non-classical monocytes (CD14+CD16+) seem to play an important role in TB, we studied the relationship between these cells and the immunological status of patients. TB patients were classified as high responders (HR-TB) or low responders (LR-TB) according to their T cell responses against a whole cell lysate of Mycobacterium tuberculosis (Mtb-Ag). Thus, LR-TB, individuals with severe disease, display a weaker immune response to Mtb compare to HR-TB, subjects with strong immunity against the bacteria. We observed that LR-TB presented higher percentages of CD14+CD16+ monocytes as compared to HR-TB and healthy donors (HD). Moreover, monocyte-like (M-MDSC) and polymorphonuclear-like MDSC (PMN-MDSC) were increased in TB patients as compared to HD. Furthermore, the proportion of M-MDSC of TB patients inversely correlated with the levels of IFN-γ ...
Frontiers in Cellular and Infection Microbiology, 2022
Alterations of myeloid cell populations have been reported in patients with tuberculosis (TB). In... more Alterations of myeloid cell populations have been reported in patients with tuberculosis (TB). In this work, we studied the relationship between myeloid-derived suppressor cells (MDSC) and monocytes subsets with the immunological responsiveness of TB patients. Individuals with active TB were classified as low responders (LR-TB) or high responders (HR-TB) according to their T cell responses against a cell lysate of Mycobacterium tuberculosis (Mtb-Ag). Thus, LR-TB, individuals with severe disease, display a weaker immune response to Mtb compare to HR-TB, subjects with strong immunity against the bacteria. We observed that LR-TB presented higher percentages of CD16 positive monocytes as compared to HR-TB and healthy donors. Moreover, monocyte-like (M-MDSC) and polymorphonuclear-like (PMN-MDSC) MDSC were increased in patients and the proportion of M-MDSC inversely correlated with IFN-γ levels released after Mtb-Ag stimulation in HR-TB. We also found that LR-TB displayed the highest perc...
El objetivo del presente estudio fue determinar el rédito diagnóstico y los factores asociados a ... more El objetivo del presente estudio fue determinar el rédito diagnóstico y los factores asociados a mayor morbimortalidad en la biopsia quirúrgica de pulmón en pacientes con enfermedad intersticial difusa. Se analizaron en forma retrospectiva los registros clínicos de 71 pacientes. Se registraron complicaciones en 16 pacientes (22.5%). La mortalidad operatoria fue 11.2%. Los pacientes en quienes la biopsia se realizó por videotoracoscopia (n = 52) y por toracotomía (n = 17) tuvieron la misma duración de estadía en terapia intensiva y de estadía hospitalaria. La tasa de complicaciones (22.2% vs. 21.0%, p = 1.0000) y la mortalidad (9.2 vs. 15.7%, p = 0.2738) no fueron diferentes. Ocho pacientes murieron dentro de los 30 días. La prevalencia de inmunosupresión (4/8 vs. 9/63, p = 0.0325) fue significativamente superior en el grupo de pacientes fallecidos. Estos pacientes tuvieron valores preoperatorios más elevados de urea (50 ± 20.1 mg/dl vs. 31.2 ± 10.3 mg/ dl, p = 0.0013) y menores valo...
El objetivo del estudio fue determinar las características clínicas de los pacientes con esclerod... more El objetivo del estudio fue determinar las características clínicas de los pacientes con esclerodermia y compromiso pulmonar y evaluar si existen factores clínicos predictores de mayor riesgo de enfermedad intersticial. Se estudiaron en forma retrospectiva 40 pacientes con esclerodermia. Fueron divididos en 2 grupos: capacidad de difusión del monóxido de carbono (DLCO) normal (n = 22) y DLCO disminuida (n = 18, 45%). Los pacientes con DLCO disminuida no fueron diferentes en edad (51.1 ± 13.5 vs. 53.5 ± 9.3 años, p = 0.5182), sexo (varones 13.6%, p = 0.6088 ), presencia de Raynaud (86.6% vs. 85%, p = 0.6272), síndrome de ojo seco (6.2% vs. 10.5%, p = 1.0000) prevalencia de enfermedad difusa (94.1% vs. 83.3%, p = 0.6026) o de dilatación esofágica. El tiempo de evolución de la enfermedad no fue diferente. La sensibilidad de la disnea para detectar una DLCO alterada fue 46.6% con una especificidad del 90% y la de la caída de la saturación de O2 (SaO2) del 71.4% y 80% respectivamente. Lo...
Prostaglandin E2 (PGE2), an active lipid compound derived from arachidonic acid, regulates differ... more Prostaglandin E2 (PGE2), an active lipid compound derived from arachidonic acid, regulates different stages of the immune response of the host during several pathologies such as chronic infections or cancer. Manipulation of PGE2 levels was proposed as an approach for countering the Type I IFN signature of tuberculosis (TB), but very limited information exists about this pathway in patients with active TB. Here, we demonstrated that PGE2 exerts a potent immunosuppressive action during the immune response of the human host against M. tuberculosis. Thus, we showed that PGE2 inhibited both lymphoproliferation and cytokine production of proinflammatory cytokines, together with a significant reduction of the surface expression of several immunological receptors in human cells. However, PGE2 promoted the autophagic flux of antigen-stimulated monocytes, even in the presence of IFNα. In this way, the attenuation of inflammation and immunopathology caused by an excessive immune response emerg...
Tuberculin skin test (TST) and IFN-γ release assays are currently used to detect Mycobacterium tu... more Tuberculin skin test (TST) and IFN-γ release assays are currently used to detect Mycobacterium tuberculosis (Mtb) infection but none of them differentiate active from latent infection (LTBI). Since improved tests to diagnose Mtb infection are required, we studied the immune response to Mtb latency antigen Rv2626c in individuals exposed to the bacteria during different periods. Tuberculosis patients (TB), TB close contacts (CC: subjects exposed to Mtb for less than three months) and healthcare workers (HW: individuals exposed to Mtb at least two years) were recruited and QuantiFERON (QFT) assay, TST and IFN-γ secretion to Rv2626c were analyzed. Twenty-two percent of the individuals assessed had discordant results between QFT and TST tests. Furthermore, QFT negative and QFT positive individuals produced differential levels of IFN-γ against Rv2626c, in direct association with their exposure period to Mtb. Actually, 91% of CC QFT negative subjects secreted low levels of IFN-γ to Rv2626c...
Dendritic cells (DCs) are a key player in the host response to the tuberculosis (TB) agent, Mycob... more Dendritic cells (DCs) are a key player in the host response to the tuberculosis (TB) agent, Mycobacterium tuberculosis (Mtb), which interfere with DC functions. However, how metabolic pathways influence DC function and activation in TB is unknown. We found that Mtb triggers both glycolysis and to a lesser extent mitochondrial respiration in human monocyte-derived DCs. This was accompanied by an increase in expression of the transcription factor HIF-1α and several glycolytic genes, dependent on TLR2 engagement by Mtb. Inhibition of either HIF-1α or glycolysis resulted in a strong alteration of the DCs migration capacities. In addition, DCs derived from monocytes of TB patients are deficient in inducing glycolysis and cell migration in response to Mtb, rescuable by induction of HIF-1α activity. Indeed, monocytes from TB patients are already highly glycolytic, differentiating into poorly migratory DCs. The data uncover a crucial role for glycolysis in DC migration and suggest that its ...
ABSTRACT Neutrophils infected with Mycobacterium tuberculosis (Mtb) predominate in tuberculosis p... more ABSTRACT Neutrophils infected with Mycobacterium tuberculosis (Mtb) predominate in tuberculosis patients’ lungs. Neutrophils phagocytose the pathogen, but the mechanism of pathogen elimination is controversial. Macroautophagy/autophagy, a crucial mechanism for several neutrophil functions, can be modulated by immunological mediators. The costimulatory molecule SLAMF1 can act as a microbial sensor in macrophages being also able to interact with autophagy-related proteins. Here, we demonstrate for the first time that human neutrophils express SLAMF1 upon Mtb-stimulation. Furthermore, SLAMF1 was found colocalizing with LC3B+ vesicles, and activation of SLAMF1 increased neutrophil autophagy induced by Mtb. Finally, tuberculosis patients’ neutrophils displayed reduced levels of SLAMF1 and lower levels of autophagy against Mtb as compared to healthy controls. Altogether, these results indicate that SLAMF1 participates in neutrophil autophagy during active tuberculosis. Abbreviations: AFB: acid-fast bacilli; BafA1: bafilomycin A1; CLL: chronic lymphocytic leukemia; DPI: diphenyleneiodonium; EVs: extracellular vesicles; FBS: fetal bovine serum; HD: healthy donors; HR: high responder (tuberculosis patient); IFNG: interferon gamma; IL1B: interleukin 1 beta; IL17A: interleukin 17A; IL8: interleukin 8; LR: low responder (tuberculosis patient); mAb: monoclonal antibody; MAP1LC3/LC3: microtubule associated protein 1 light chain 3; MAPK: mitogen-activated protein kinase; MAPK1/ERK2: mitogen-activated protein kinase 1; MAPK14/p38: mitogen-activated protein kinase 14; Mtb: Mycobacterium tuberculosis; Mtb-Ag: Mycobacterium tuberculosis, Strain H37Rv, whole cell lysate; NETs: neutrophils extracellular traps; PPD: purified protein derivative; ROS: reactive oxygen species; PIK3C3/VPS34: phosphatidylinositol 3-kinase catalytic subunit type 3; SLAMF1: signaling lymphocytic activation molecule family member 1; TB: tuberculosis; TLR: toll like receptor
pacientes con iniciacion aguda la mortalidad fue significativamente mas elevada (36.3% vs. 7.1%, ... more pacientes con iniciacion aguda la mortalidad fue significativamente mas elevada (36.3% vs. 7.1%, p = 0.0223). La biopsia aporto un diagnostico especifico en 100% de los pacientes y cambio la estrategia terapeutica en 66.7%. En conclusion, la biopsia de pulmon por via toracoscopica es un procedimiento util y seguro en los pacien- tes con enfermedad intersticial difusa del pulmon. Sin embargo, en el grupo de pacientes inmunocomprometidos, con cuadros de presentacion aguda y con insuficiencia respiratoria preoperatoria, la mortalidad es elevada y de- ben balancearse muy criticamente los riesgos contra los beneficios en ese grupo de enfermos. Palabras clave: biopsia de pulmon, biopsia toracoscopica, enfermedad intersticial pulmonar, neumonia intersticial usual Abstract Lung biopsy for the diagnosis of interstitial lung disease. The objective of this study was to determine the morbidity, mortality and diagnostic yield of video assisted thoracoscopy (VATS) and thoracotomy lung biopsy in i...
The objective of this study was to determine clinical predictors of interstitial lung disease in ... more The objective of this study was to determine clinical predictors of interstitial lung disease in patients with systemic sclerosis (SSc) and pulmonary involvement as defined by presence of a decreased diffusing capacity for carbon monoxide (DLCO). Forty subjects with SSc were retrospectively evaluated. Patients were categorized according to their level of DLCO (< o > or = 80% of predicted). Sensitivity of dyspnea to detect a decreased DLCO was 46.6% and specificity 90%, whereas oxygen desaturation showed a sensitivity of 71.4% and a specificity of 80%. Patients with decreased DLCO (n = 18) were not different in age (51.1 +/- 13.5 vs. 53.5 +/- 9.3 y, p = 0.5182), sex (male 13.6%, p = 0.6088), prevalence of Raynaud (86.6% vs. 85%, p = 0.6272), sicca syndrome (6.2% vs. 10.5% p = 1.0000) diffuse cutaneous involvement (94.1% vs. 83.3%, p = 0.6026) or esophageal dilatation. The duration of symptoms since diagnosis was no different. Prevalence of pulmonary hypertension assessed by Dop...
Lung involvement in systemic sclerosis. The objective of this study was to determine clinical pre... more Lung involvement in systemic sclerosis. The objective of this study was to determine clinical predictors of interstitial lung disease in patients with systemic sclerosis (SSc) and pulmonary involvement as defined by presence of a decreased diffusing capacity for carbon monoxide (DLCO). Forty subjects with SSc were retrospectively evaluated. Patients were categorized according to their level of DLCO (< o ≥ 80% of predicted). Sensitivity of dyspnea to detect a decreased DLCO was 46.6% and specificity 90%, whereas oxygen desaturation showed a sensitivity of 71.4% and a specificity of 80%. Patients with decreased DLCO (n = 18) were not different in age (51.1 ± 13.5 vs. 53.5 ± 9.3 y, p = 0.5182), sex (male 13.6%, p = 0.6088), prevalence of Raynaud (86.6% vs. 85%, p = 0.6272), sicca syndrome (6.2% vs. 10.5% p = 1.0000) diffuse cutaneous involvement (94.1% vs. 83.3%, p = 0.6026) or esophageal dilatation. The duration of symptoms since diagnosis was no different. Prevalence of pulmonary ...
Prostaglandin E2 (PGE2), an active lipid compound derived from arachidonic acid, regulates differ... more Prostaglandin E2 (PGE2), an active lipid compound derived from arachidonic acid, regulates different stages of the immune response of the host during several pathologies such as chronic infections or cancer. In fact, manipulation of PGE2 levels was proposed as an approach for countering the Type I IFN signature of tuberculosis (TB). However, very limited information regarding the PGE2 pathway in patients with active TB is currently available. In the present work, we demonstrated that PGE2 exerts a potent immunosuppressive action during the immune response of the human host against Mycobacterium tuberculosis (Mtb) infection. Actually, we showed that PGE2 significantly reduced lymphoproliferation, the production of proinflammatory cytokines, and the surface expression of several immunological receptors. On the other hand, PGE2 promoted autophagy in monocytes and neutrophils cultured with Mtb antigens. These results suggest that PGE2 might be attenuating the excessive inflammatory immu...
The objective of this study was to determine the morbidity, mortality and diagnostic yield of vid... more The objective of this study was to determine the morbidity, mortality and diagnostic yield of video assisted thoracoscopy (VATS) and thoracotomy lung biopsy in interstitial lung disease (ILD). Clinical records of 71 patients were retrospectively analyzed. There was no difference in mean hospital stay, intensive care unit stay and duration of chest tube drainage in patients with VATS (n = 52) compared with those undergoing open thoracotomy (n = 17). Complications rate (22.2% vs. 21.0%, p = 1.0000) and operating mortality (9.2 vs. 15.7%, p = 0.2738) were also similar. Overall, complications occurred in 16 patients (22.5%). Thirty-day mortality rate was 11.2% (n = 8). Prevalence of immunosupression (4/8 vs. 9/63, p = 0.0325) was significantly higher in the group of patients who died. No surviving patients had higher values of plasmatic urea (50 +/- 20.1 mg/dl vs. 31.2 +/- 10.3 mg/dl, p = 0.0013) or lower values of preoperative oxygen saturation (SaO2): 82.7 +/- 14.8% vs. 92.8 +/- 3.4%,...
Alterations of myeloid cell populations have been reported in patients with tuberculosis (TB). Si... more Alterations of myeloid cell populations have been reported in patients with tuberculosis (TB). Since myeloid-derived suppressor cells (MDSC) and non-classical monocytes (CD14+CD16+) seem to play an important role in TB, we studied the relationship between these cells and the immunological status of patients. TB patients were classified as high responders (HR-TB) or low responders (LR-TB) according to their T cell responses against a whole cell lysate of Mycobacterium tuberculosis (Mtb-Ag). Thus, LR-TB, individuals with severe disease, display a weaker immune response to Mtb compare to HR-TB, subjects with strong immunity against the bacteria. We observed that LR-TB presented higher percentages of CD14+CD16+ monocytes as compared to HR-TB and healthy donors (HD). Moreover, monocyte-like (M-MDSC) and polymorphonuclear-like MDSC (PMN-MDSC) were increased in TB patients as compared to HD. Furthermore, the proportion of M-MDSC of TB patients inversely correlated with the levels of IFN-γ ...
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