Introdução: Profissionais de saúde foram os indivíduos que sofreram constantemente os impactos da COVID-19 sendo considerados prioridade para a vacinação no Brasil. A proteção induzida pelas vacinas ...disponíveis contra o vírus baseia-se principalmente na produção de anticorpos. Esses anticorpos geralmente bloqueiam a interação do vírus com seu receptor celular ou impedem as alterações conformacionais necessárias para a fusão do vírus com a membrana celular. Objetivo: Estudar a resposta à vacina CoronaVac em profissionais da saúde, avaliando a resposta anticórpica, e a resposta de células T. Métodos: Foi realizada coleta de sangue para separação das células mononucleares do sangue periférico (PMBC) por gradiente de densidade Ficoll-Hypaque. Estas células foram transferidas para placa de cultura na concentração de 2 × 105 células/poço, por 18 horas, em duplicata nas seguintes condições: sem estímulo, estimuladas com mitógenos, estimuladas com pool de peptídeos de SARS-CoV-2, nos poços para avaliação de citocinas foi acrescido Brefeldina A. Após estímulo as células foram transferidas para tubos de citometria, e marcadas para: avaliação de resposta celular com CD3, CD4, CD8, Interferon-γ (INF-γ) e CD38. As células foram adquiridas em citômetro de fluxo LSR Fortessa. Resultados: Apenas no grupo R, os linfócitos TCD8 mostraram maior expressão de CD38 quando estimulados com o pool de peptídeos. A frequência de produtores de INF- γ e não produtores de INF- γ foi semelhante (75.9 % e 77.1%). No grupo NR a produção de INF- γ ocorreu em maior parte concomitantemente por linfócitos TCD4 e TCD8, diferente do grupo R que demonstrou produção semelhante seja por apenas um ou dois tipos de linfócitos T. Conclusão: A produção ou não de anticorpos não parece ter relação direta com a secreção de INF-γ ou expressão de CD38 por linfócitos T. Não houve diferença significativa na produção de INF- γ entre os grupos R e NR.
Objectives: To describe the clinical and histopathological information of oral squamous cell carcinomas an oral pathology clinic of a private university in Rio de Janeiro state, Brazil (1998−2017) ...and to evaluate the immunoexpression of some inflammatory markers (nterferon-gamma, cluster of differentiation 57, and cluster of differentiation 68). Methods: Clinical data were collected and histopathological evaluations of 183 oral squamous cell carcinomas were performed at an oral pathology clinic of a private university in Rio de Janeiro state, Brazil (1998−2017). Twenty-two paraffin blocks underwent immunohistochemistry to measure the Interferon-gamma, cluster of differentiation 57, and cluster of differentiation 68 expressions and positivity, and were classified as negative/focal, weak/moderate, or strong. Results: Thereabout 81% of the sample were male and 57% Caucasian. The average age was 58.6 years. Tongue cancers were the most prevalent (36.6%) and 48.1% had a moderately differentiated oral squamous cell carcinomas. Interferon-gamma was expressed in all cases, and 91% had the maximum degree of marking. The cluster of differentiation 68 expression had a maximum degree in 41% of the tumours, and surprisingly all of them in concomitance with the maximum Interferon-gamma-markings. cluster of differentiation 57 was strongly expressed in 45.5% of the sample. Conclusion: Oral squamous cell carcinomas was more frequent in Caucasians, in their fifth decade of life, and located on the tongue. The Interferon-gamma expression was observed in all cases, its role in the development of tumours and the concomitant expression of cluster of differentiation 68 suggests a possible differentiation for the M2 phenotype of tumours and a consequently a poor prognosis.
Background The intimal hyperplasia (IH) and vascular remodelling that follows endovascular injury, for instance after post-angioplasty re-stenosis, results in downstream ischaemia and progressive end ...organ damage. Interferon gamma (IFNγ) is known to play a critical role in this process. In mouse models we have previously shown that fibrocytes expressing tissue factor (TF) are recruited early to the site of injury. Through thrombin generation and protease activated receptor-1 (PAR-1) activation, fibrocytes secrete angiopoietin-2, stimulate neointimal cell proliferation, inhibit apoptosis and induce CXCL-12 production, all of which contribute to the progressive IH that then develops. In this study we investigated the relationship between TF, angiopoietin-2 and IFNγ. Methods and results IH developing in carotid arteries of wild-type mice 4 weeks after endoluminal injury contained a significant proportion of IFNγ+ fibrocytes and macrophages, which we show, using a previously defined adoptive transfer model, were derived from circulating CD34+ cells. IH did not develop after injury in IFNγ-deficient mice, except after transplantation of WT bone marrow or adoptive transfer of WT CD34+ cells. In vitro , CD34+ cells isolated from post-injury mice did not express IFNγ, but this was induced when provided with FVIIa and FX, and enhanced when prothrombin was also provided: In both cases IFNγ secretion was TF-dependent and mediated mainly through protease activated PAR-1. IFNγ was predominantly expressed by fibrocytes. In vivo , all IFNγ+ neointimal cells in WT mice co-expressed angiopoietin-2, as did the small numbers of neointimal cells recruited in IFNγ-/- mice. Adoptively transferred WT CD34+ cells treated with either an anti-TIE-2 antibody, or with siRNA against angiopoetin-2 inhibited the expression of IFNγ and the development of IH. Conclusion TF-dependent angiopoietin-2 production by newly recruited fibrocytes, and to a lesser extent macrophages, switches on IFNγ expression, and this is necessary for the IH to develop. These novel findings enhance our understanding of the pathophysiology of IH and expose potential targets for therapeutic intervention.
Adoptive transfer of T cells genetically engineered to express chimeric antigen receptors (CAR) has demonstrated striking efficacy for the treatment of several hematological malignancies, including ...B-cell lymphoma, leukemia, and multiple myeloma. However, CAR T-cell efficacy has been very limited in most solid tumors. In this context, it is of paramount importance to understand the determinants that condition CAR T-cell success versus failure. To control tumor growth, CAR T cells need to form conjugates with their targets
via
the assembly of an immunological synapse. Here, we review recent advances showing that the adhesion between CAR T cells and cancer cells from solid tumors strengthens over time in an IFNγ- and ICAM-1-dependent manner, resulting in CAR T cell-mediated killing. We discuss how these findings can be exploited to increase the efficacy of the CAR T-cell strategy against solid tumors.
Long-term changes in the immune system of successfully treated people living with HIV (PLHIV) remain incompletely understood. In this study, we assessed 108 white blood cell (WBC) populations in a ...cohort of 211 PLHIV on stable antiretroviral therapy and in 56 HIV-uninfected controls using flow cytometry. We show that marked differences exist in T cell maturation and differentiation between PLHIV and HIV-uninfected controls: PLHIV had reduced percentages of CD4+ T cells and naïve T cells and increased percentages of CD8+ T cells, effector T cells, and T helper 17 (Th17) cells, together with increased Th17/regulatory T cell (Treg) ratios. PLHIV also exhibited altered B cell maturation with reduced percentages of memory B cells and increased numbers of plasmablasts. Determinants of the T and B cell composition in PLHIV included host factors (age, sex, and smoking), markers of the HIV reservoir, and CMV serostatus. Moreover, higher circulating Th17 percentages were associated with higher plasma concentrations of interleukin (IL) 6, soluble CD14, the gut homing chemokine CCL20, and intestinal fatty acid binding protein (IFABP). The changes in circulating lymphocytes translated into functional changes with reduced interferon (IFN)- γ responses of peripheral blood mononuclear cells to stimulation with
and
In conclusion, this comprehensive analysis confirms the importance of persistent abnormalities in the number and function of circulating immune cells in PLHIV on stable treatment.
To evaluate the frequency of and factors associated with indeterminate interferon-gamma release assay (IGRA) results in people living with HIV/AIDS (PLWHA).
We tested 81 PLWHA in the central-west ...region of Brazil, using the tuberculin skin test and an IGRA. Information on sociodemographic and clinical variables was gathered through the use of questionnaires and from medical records. The association of those variables with indeterminate results was analyzed by calculating the adjusted ORs in a multivariate logistic regression model. Concordance was evaluated by determining the kappa statistic.
Among the 81 patients evaluated, the tuberculin skin test results were positive in 18 (22.2%) of the patients, and the IGRA results were positive in 10 (12.3%), with a kappa of 0.62. The IGRA results were indeterminate in 22 (27.1%) of the patients (95% CI: 17.8-38.1%). The odds of obtaining indeterminate results were significantly higher in smokers (adjusted OR = 6.0; 95% CI: 1.4-26.7) and in samples stored for less than 35 days (adjusted OR = 14.0; 95% CI: 3.1-64.2). Patients with advanced immunosuppression (CD4+ T-cell count < 200 cells/mm3) were at a higher risk for indeterminate results (OR adjusted for smoking and inadequate duration of sample storage = 4.7; 95% CI: 0.91-24.0), although the difference was not significant.
The high prevalence of indeterminate results can be a major limitation for the routine use of IGRAs in PLWHA. The need to repeat the test increases its costs and should be taken into account in cost-effectiveness studies. The processing of samples can significantly alter the results.
Avaliar a frequência de resultados indeterminados de um interferon-gamma release assay (IGRA, ensaio de liberação de interferon-gama) e os fatores relacionados com esses resultados em pessoas vivendo com HIV/AIDS (PVHA).
Foram avaliadas 81 PVHA na região Centro-Oeste do Brasil, por meio do teste tuberculínico e de um IGRA. Informações a respeito de variáveis sociodemográficas e clínicas foram obtidas por meio de questionários e prontuários médicos. A relação entre essas variáveis e os resultados indeterminados foi avaliada por meio do cálculo da OR ajustada em um modelo de regressão logística multivariada. A concordância foi avaliada por meio do coeficiente kappa.
Os resultados do teste tuberculínico e do IGRA foram positivos em 18 (22,2%) e 10 (12,3%), respectivamente, dos 81 pacientes avaliados (κ = 0,62). O resultado do IGRA foi indeterminado em 22 (27,1%) dos pacientes (IC95%: 17,8-38,1%). A chance de resultados indeterminados foi significativamente maior em fumantes (OR ajustada = 6,0; IC95%: 1,4-26,7) e em amostras armazenadas durante menos de 35 dias (OR ajustada = 14,0; IC95%: 3,1-64,2). Pacientes com imunossupressão avançada (contagem de células T CD4+ < 200 células/mm3) apresentaram maior risco de resultados indeterminados (OR ajustada para tabagismo e tempo inadequado de armazenamento das amostras = 4,7; IC95%: 0,91-24,0), embora a diferença não tenha sido significativa.
A alta prevalência de resultados indeterminados pode ser um grande obstáculo ao uso rotineiro de IGRAs em PVHA. A necessidade de repetir o teste aumenta seu custo e deve ser levada em conta em estudos da relação entre custo e eficácia. O processamento das amostras pode alterar significativamente os resultados.
In individuals with asthma, obesity induces the production of leptin and is associated with disease severity. Our objective was to evaluate the levels of serum leptin and their effect on Th1/Th2 ...balance in obese and non-obese children with asthma, as well as to investigate the association between serum leptin levels and clinical outcomes.
We evaluated 50 atopic children with physician-diagnosed moderate-to-severe persistent asthma and 20 controls. The children with asthma were divided into two groups, by body mass index percentile: obese (n = 25) and non-obese (n = 25). From all subjects, we collected peripheral blood samples in order to determine the levels of leptin, IFN-γ, and IL-4. Asthma severity was assessed by an asthma symptom score, and the results were correlated with the parameters studied.
Serum leptin levels were significantly higher in the obese asthma group than in the non-obese asthma group, as well as being significantly higher in the children with asthma than in the controls, whereas IFN-γ levels were significantly higher and IL-4 levels were significantly lower in the obese asthma group than in the non-obese asthma group. In addition, the obese asthma group showed higher asthma symptom scores and significantly lower FEV1 (% of predicted) than did the non-obese asthma group. There was a significant positive correlation between leptin and IFN-γ levels only in the obese asthma group.
Although leptin is involved in the pathogenesis of asthma in obese and non-obese children, its effect is more pronounced in the former. In the presence of high leptin levels, only obese children with asthma exhibited Th1 polarization, with higher IFN-γ levels and greater asthma severity.
Objective To explore the value of adenosine deaminase (ADA) activity, interferon-gamma (IFN-γ) and IFN-γ induced protein of 10kD (IP-10) levels in pleural effusion for the diagnosis of tuberculous ...pleuritis. Methods ADA activity, IFN-γ and IP-10 levels in pleural effusion were determined in sixty-three patients with tuberculous pleuritis and 50 patients with malignant pleural effusion. Results The mean levels of ADA, IFN-γ and IP-10 in the tuberculous pleural effusion were significantly higher than those in malignant pleural effusion (P<0.01). When 45U/L was regarded as cut off value for ADA, the sensitivity, specificity and diagnostic odds ratio in the diagnosis of tuberculous pleurisy were 71.4%, 94.0% and 39.17 respectively. When 138.5pg/ml was regarded as cut off value for IFN-γ in tuberculous pleural effusion, the sensitivity, specificity and diagnostic odds ratio were 93.7%, 82.0% and 67.19 respectively. When 9.21μg/ml was regarded as cut off value for IP-10 in tuberculous pleural effusion, the sensitiv
To evaluate the accuracy of an interferongamma release assay (QuantiFERON-TB Gold in Tube) for diagnosing Mycobacterium tuberculosis infection in a young pediatric population.
195 children previously ...vaccinated with BCG were evaluated, being 184 healthy individuals with no clinical or epidemiological evidence of mycobacterial infection, and 11 with Mycobacterium tuberculosis infection, according to clinical, radiological, and laboratory parameters. A blood sample was obtained from each child and processed according to the manufacturer's instructions. The assay performance was evaluated by a Receiver Operating Characteristic (ROC) curve.
In the group of 184 non-infected children, 130 (70.6%) were under the age of four years (mean age of 35 months). In this group, 177 children (96.2%) had negative test results, six (3.2%) had indeterminate results, and one (0.5%) had a positive result. In the group of 11 infected children, the mean age was 58.5 months, and two of them (18%) had negative results. The ROC curve had an area under the curve of 0.88 (95%CI 0.82-0.92; p<0.001), disclosing a predictive positive value of 81.8% for the test (95%CI 46.3-97.4). The assay sensitivity was 81.8% (95%CI 48.2-97.2) and the specificity was 98.8% (95%CI 96-99.8).
In the present study, the QuantiFERON-TB Gold in Tube performance for diagnosing M. tuberculosis infection was appropriate in a young pediatric population.
We report a rare case in a female infant (age, 3.5 months) with primary immunodeficiency (IFN-γ/IL-12 pathway defect) who presented with suppurative lymphadenitis after Mycobacterium bovis BCG ...vaccination. The strain of M. bovis BCG identified was found to be resistant to isoniazid and rifampin. The patient was treated with a special pharmacological regimen involving isoniazid (in a limited, strategic manner), ethambutol, streptomycin, and IFN-γ, after which there was complete resolution of the lesions.
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