Viral infections in interferon-gamma receptor deficiency.

Interferon-gamma receptor deficiency is a recently described immunodeficiency that is associated with onset of severe mycobacterial infections in childhood. We describe the occurrence of symptomatic and often severe viral infections in 4 patients with interferon-gamma receptor deficiency and mycobacterial disease. The viral pathogens included herpes viruses, parainfluenza virus type 3, and respiratory syncytial virus. We conclude that patients with interferon-gamma receptor deficiency and mycobacterial disease have increased susceptibility to some viral pathogens

Interferon-gamma and interleukin-10 production by mononuclear cells from patients with advanced head and neck cancer

OBJECTIVE: This study aims to evaluate the production of interferon-gamma and interleukin-10 by stimulated peripheral blood mononuclear cells isolated from patients with supraglottic laryngeal cancer before and after surgical treatment. METHODS: Fourteen patients with advanced supraglottic laryngeal cancer were studied. Cultures of peripheral blood mononuclear cells isolated during the preoperative and late postoperative periods were stimulated with concanavalin A and Bacille Calmette-Guerin, and the supernatant concentrations of interferon-gamma and interleukin-10 were measured. RESULTS: For non-stimulated cultures, the interferon-gamma levels produced by the preoperative period and the late postoperative period cultures were lower than the levels produced by the control group cultures. The interferon-gamma levels after stimulation with concanavalin A were higher in the late postoperative period cultures than in the preoperative evaluation cultures. Stimulation with Bacille Calmette-Guerin led to the production of similar levels of interferon-gamma and interleukin-10 by all cultures; thus, stimulation increased the levels of interferon-gamma produced by both the preoperative and postoperative cultures relative to the levels produced by the corresponding unstimulated cultures. CONCLUSION: Patients with advanced supraglottic laryngeal cancer exhibit an in vitro deficiency in interferongamma secretion by mononuclear cells. Stimulated cells seem to recover this function during the postoperative period

Interferon-gamma and interleukin-10 production by mononuclear cells from patients with advanced head and neck cancer

OBJECTIVE: This study aims to evaluate the production of interferon-gamma and interleukin-10 by stimulated peripheral blood mononuclear cells isolated from patients with supraglottic laryngeal cancer before and after surgical treatment. METHODS: Fourteen patients with advanced supraglottic laryngeal cancer were studied. Cultures of peripheral blood mononuclear cells isolated during the preoperative and late postoperative periods were stimulated with concanavalin A and Bacille Calmette-Guerin, and the supernatant concentrations of interferon-gamma and interleukin-10 were measured. RESULTS: For non-stimulated cultures, the interferon-gamma levels produced by the preoperative period and the late postoperative period cultures were lower than the levels produced by the control group cultures. The interferon-gamma levels after stimulation with concanavalin A were higher in the late postoperative period cultures than in the preoperative evaluation cultures. Stimulation with Bacille Calmette-Guerin led to the production of similar levels of interferon-gamma and interleukin-10 by all cultures; thus, stimulation increased the levels of interferon-gamma produced by both the preoperative and postoperative cultures relative to the levels produced by the corresponding unstimulated cultures. CONCLUSION: Patients with advanced supraglottic laryngeal cancer exhibit an in vitro deficiency in interferongamma secretion by mononuclear cells. Stimulated cells seem to recover this function during the postoperative period

Therapeutic potential of interferon-gamma in tuberculosis

Tuberculosis is one of the critical health problems worldwide. The search for ways to improve the results of tuberculosis treatment and overcome drug resistance lies in understanding the pathogenesis of the development of the infectious process. The interferon system, particularly the role of interferon-gamma, has been identified as the main link in the immune response in tuberculosis. The clinical efficacy of interferon-gamma has been studied and evaluated in clinical trials since the end of the last century. There was obtained evidence of the clinical efficacy of interferon-gamma as part of complex therapy. Recent experimental data make it possible to consider interferon-gamma as a promising therapeutic option for the treatment of multidrug-resistant tuberculosis as part of complex therapy worthy of further studies

Use of interferon gamma release assay to assess latent tuberculosis infection among healthcare workers in Hong Kong

Key Messages 1. Overall baseline interferon gamma release assay positivity was 20.7%. 2. The conversion to interferon gamma release assay positivity at 3 months was 8.85% in the exposed group and 4.54% in the non-exposed group using the conventional cut-off of 0.35 IU/mL. 3. When grey zone results (0.2I-0.7 IU/mL) were included, the proportion of non-specific conversions and reversions could be reduced. 4. Interferon gamma release assay can be an adjunct tool in contact investigation of latent tuberculosis infection in healthcare workers.published_or_final_versio

TUBERCULOSIS IN CHILDREN: NEW FORMS OF DIAGNOSIS

Introdução: A tuberculose ainda é um grave problema de saúde pública em Portugal. Para diminuir o número de casos de tuberculose ativa em populações de baixa e intermédia incidência, é necessário um diagnóstico rápido e um tratamento eficaz. A prova tuberculínica é o método de rastreio recomendado, mas as suas limitações são conhecidas. Em 2001, foi aprovado o primeiro de diversos interferon gamma release assays, considerados úteis no diagnóstico de infeção latente por Mycobacterium tuberculosis, amplamente utilizados na abordagem da tuberculose nos adultos. Objectivos: Sumarizar a informação disponível sobre os interferon gamma release assays, nomeadamente no que diz respeito à técnica; às vantagens no diagnóstico da infeção latente por Mycobacterium tuberculosis; à sensibilidade e especificidade quando aplicados à população pediátrica; à caracterização de fatores interferentes; e ao seu significado na monitorização do tratamento com antituberculosos. Desenvolvimento: Os interferon gamma release assays são testes imunologicamente seletivos, desenvolvidos com base em antigénios do Mycobacterium tuberculosis. Têm sido aplicados na Pediatria, em regiões com diferentes taxas de prevalência de tuberculose, de forma a compará-los com a prova tuberculínica relativamente à sensibilidade e especificidade. Conclusões: A utilização destes testes como forma de rastreio em Pediatria apresenta limitações. São necessários estu- dos a nível nacional que permitam mostrar de que forma a prova tuberculínica e os interferon gamma release assays se devem articular. Atualmente, os interferon gamma release assays ape- nas complementam a prova tuberculínica

Kadar Interferon Gamma pada Kontak Serumah dengan Penderita Tuberkulosis

Menurut World Health Organization sekitar sepertiga penduduk dunia telah terinfeksi kuman tuberkulosis dan deteksi dini pada kontak serumah dengan penderita memungkinkan upaya pengobatan dan pencegahan dilakukan dengan efektif. Penelitian ini bertujuan untuk membandingkan hasil pemeriksaan tes Mantoux dengan pemeriksaan serologis kadar interferon gamma (IFN - γ) pada kelompok kontak serumah dengan penderita tuberkulosis yang mempunyai hasil pemeriksaan basil tahan asam (BTA) positif. Penelitian ini menggunakan desain kohort pada kelompok terpajan dan tidak terpajan pada penderita tuberkulosis (umur > 15 tahun). Pemilihan subjek dilakukan secara acak sederhana dan jumlah yang digunakan adalah 34 orang pada masing-masing kelompok. Penelitian ini menggunakan tes Mantoux selain observasi kadar IFN-γ. Analisis data menggunakan chi square dan tes Man Whitney. Penelitian tahun pertama menunjukkan hasil tes Mantoux positif pada kelompok terpajan sebesar 79,4% dan 5,9% pada kelompok tidak terpajan. Rata-rata kadar IFN - γ pada kelompok yang terpajan penderita tuberkulosis adalah 5,32 pg/ml sedangkan pada kelompok yang tidak terpajan sebesar 1,1 pg/ml. Ada hubungan yang bermakna antara status paparan dengan hasil tes Mantoux (nilai p = 0,0001 dan x2= 34,631). Ada perbedaan rata-rata kadar IFNγ secara bermakna antara kelompok terpajan dengan kelompok yang tidak terpajan (nilai p = 0,0001). Masih diperlukan penelitian lebih lanjut untuk mengikuti perkembangan IFN-γ berdasarkan status paparan untuk mengetahui pola dan cut off point pada kontak serumah dengan penderita tuberkulosis.Kata kunci: Kadar interferon gamma, kontak serumah, penderita tuberkulosisWorld Health Organization estimated that one third people worldwide were infected with mycobacterium tuberculosis. An early diagnosis and prompt treatment of possible pulmonary tuberculosis infection should be made for close contacts (housemate contacts) of patient with tuberculosis. The purpose of this research is to analyze the differences levels of IFN-γ and Tuberculine Skin Test (TST) on the housemate contacts and non-house- mate contacts with patients of tuberculosis. Cohort study performed on the housemate contacts and non-housemate contacts with patients of tuberculosis (age > 15 years old). We collected data with simple random sampling on 68 persons (34 exposed and 34 unexposed). Bivariate associations were described using chi square and Man Whitney test. During the first year of study, 76,4% of exposed persons with TST positive and 5,9% of unexposed persons. Average levels of IFN - γ in exposed persons 5,32 pg/ml, whereas in other groups 1,1 pg/ml. There is relationship between exposure sta- tus and unexposed status of TST (p value = 0,0001 and x2 = 34,631). There are differences in mean levels of IFN - γ between group exposed and unexposed (p value = 0,0001). Further research will be needed to keep abreast of IFN - γ level on the basis of exposure status to know the cut off point on the housemate contacts with patients of tuberculosis

Understanding pathogenic and physiological T follicular helper cell formation

T follicular helper (Tfh) cells localize to follicles where they provide growth and selection signals to mutated germinal center (GC) B cells, thus promoting their differentiation into high affinity long-lived plasma cells and memory B cells. T-dependent B cell differentiation also occurs extrafollicularly, giving rise to unmutated plasma cells that are important for early protection against microbial infections. Bcl-6 expression in T cells has been shown to be essential for the formation of Tfh cells and GC B cells, but little is known about its requirement in physiological extrafollicular antibody responses. We use several mouse models in which extrafollicular plasma cells can be unequivocally distinguished from those of GC origin, combined with antigen-specific T and B cells, to show that the absence of T cell-expressed Bcl-6 significantly reduces T-dependent extrafollicular antibody responses. Bcl-6+ T cells appear at the T-B border soon after T cell priming and before GC formation, and these cells express low amounts of PD-1. Their appearance precedes that of Bcl-6+PD-1hi T cells, which are found within GC. IL-21 acts early to promote both follicular and extrafollicular antibody responses. In conclusion, Bcl6+ T cells are necessary at B cell priming in order to form extrafollicular antibody responses, and these pre-GC Tfh cells can be distinguished phenotypically from GC Tfh cells. Overactivity of the GC pathway due to accumulation of Tfh cells causes autoimmunity, underscoring the need to understand the factors that control Tfh homeostasis. Here, we have identified posttranscriptional repression of interferon-gamma (Ifng) mRNA as a novel mechanism to limit Tfh cell formation. Using the sanroque lupus model, we have shown that decreased Ifng mRNA decay caused excessive interferon-gamma signaling in T cells and led to accumulation of Tfh cells, spontaneous GC, autoantibody formation and nephritis. Unlike ICOS and T-bet deficiency that failed to rescue several autoimmune manifestations, interferon-gamma receptor deficiency completely prevented lupus development. Interferon-gamma blockade after disease onset reduced Tfh cells and autoantibodies, demonstrating that interferon-gamma overproduction was required to sustain lupus-associated pathology. Increased interferon-gamma signaling caused Bcl-6 overexpression in Tfh cells and their precursors. This novel link between interferon-gamma and aberrant Tfh formation provides a rationale for interferon-gamma blockade in lupus patients with an overactive Tfh cell-associated pathway

Determination of interferon gamma associated with malaria parasitaemia among patients attending selected hospitals in Zaria, Kaduna State, Nigeria

BackgroundMalaria has been recognized as a severe and life- threatening illness for thousands of years. It is still one of the most common diseases affecting humans worldwide. Results gathered in primates challenged by Plasmodium falciparum and, to some extent, in humans, point to interferon gamma as a possible immune mediator or at least a surrogate marker significantly associated with protection against Plasmodium falciparum and actually, the only surrogate available to-date.AimThis study was aimed at determining malaria parasitaemia and interferon gamma concentration among patients attending selected hospitals in Zaria, Kaduna State, Nigeria.MethodsFour hundred blood samples were collected from four hospitals in Zaria, Kaduna State.The samples were microscopically screened for malaria parasites. The concentrations of interferon gamma were determined using ELISA, and the results obtained were analysed using Chi square.ResultsOnly the ring trophozoites of Plasmodium falciparum were observed in the infected samples. In the whole study population, males had a higher parasitaemia than females.The individuals with Plasmodium falciparum infection had the highest mean concentrations of interferon gamma with 121.32pg/ml than those in the negative control group, that is, those without the infection (75.69pg/ml). There was no statistically significant difference (p=0.079).ConclusionThis study shows a higher Plasmodium falciparumparasitaemia in males than females, with a relatively higher concentration of interferon gamma in the group with parasitamia than the control group

The effect of abrupt weaning of suckler calves on the plasma concentrations of cortisol, catecholamines, leukocyte, acute-phase proteins and in vitro interferon-gamma production

End of project reportThe objective of this study was to examine the effect of abrupt weaning (inclusive of social group disruption and maternal separation) on the physiological mediators of stress and measures of immune function. Thirty-eight male and 38 female continental calves were habituated to handling for two weeks prior to bleeding. Calves were blocked on sex, weight and breed of dam and randomly assigned, within block, to either a control (cows remain with calves) or abruptly weaned group (calves removed from cows). Animals were separated into the respective treatment groups at weaning (0 h). Calves were bled at – 168 h, 6 h (males only), 24 h, 48 h and 168 h post weaning. At each sampling time an observer scored the behavioural reaction of calves to sampling. Blood samples were analysed for cortisol, catecholamine concentrations (not sampled at –168 h) and in vitro interferon-gamma production, neutrophil :lymphocyte ratio and acute phase protein concentrations. All continuous data were analysed using a split-plot ANOVA, except that collected at 6 h, which was analysed using a single factor ANOVA model. The effects of weaning, calf sex and time and respective interactions were described. Disruption of the established social groups at 0 h, increased (p<0.001) the plasma cortisol concentration and neutrophil: lymphocyte ratio and reduced the leukocyte concentration (p<0.001) and the in vitro interferon-gamma response to the mitogen concanavalin-A (p<0.001) and keyhole limpet haemocyanin (p<0.001) for weaned and control animals, when compared with –168h. Plasma adrenaline and noradrenaline concentrations were not affected by group disruption. There was no effect of weaning or sex on calf behavioural reaction to handling during blood sampling. Plasma cortisol and adrenaline concentrations were not affected by weaning or sex. Plasma noradrenaline concentration was influenced by weaning x sex (p<0.05) and time x sex (p<0.05). The response increased for male calves with weaning and increased with each sampling time post weaning. For heifers the response was not affected by weaning and plasma concentrations decreased at 168 h post weaning. There was no effect of weaning or sex on leukocyte concentration. The neutrophils : lymphocyte ration increased post weaning (p<0.01) and was affected by sex (p<0.05). Weaning decreased (p<0.05) the in vitro interferon-gamma response to the antigen KLH. There was a time x weaning x sex (p<0.05) interaction for fibrinogen concentration but no effect of treatment on haptoglobin concentration. Abrupt weaning increased plasma cortisol and nor-adrenaline concentrations, which was accompanied by attenuation of in vitro interferon gamma production to novel mitogen and antigen complexes up to 7 days post weaning.European Union Structural Funds (EAGGF