Low Penetrance, Broad Resistance, and Favorable Outcome of Interleukin 12 Receptor β1 Deficiency: Medical and Immunological Implications

The clinical phenotype of interleukin 12 receptor β1 chain (IL-12Rβ1) deficiency and the function of human IL-12 in host defense remain largely unknown, due to the small number of patients reported. We now report 41 patients with complete IL-12Rβ1 deficiency from 17 countries. The only opportunistic infections observed, in 34 patients, were of childhood onset and caused by weakly virulent Salmonella or Mycobacteria (Bacille Calmette-Guérin -BCG- and environmental Mycobacteria). Three patients had clinical tuberculosis, one of whom also had salmonellosis. Unlike salmonellosis, mycobacterial infections did not recur. BCG inoculation and BCG disease were both effective against subsequent environmental mycobacteriosis, but not against salmonellosis. Excluding the probands, seven of the 12 affected siblings have remained free of case-definition opportunistic infection. Finally, only five deaths occurred in childhood, and the remaining 36 patients are alive and well. Thus, a diagnosis of IL-12Rβ1 deficiency should be considered in children with opportunistic mycobacteriosis or salmonellosis; healthy siblings of probands and selected cases of tuberculosis should also be investigated. The overall prognosis is good due to broad resistance to infection and the low penetrance and favorable outcome of infections. Unexpectedly, human IL-12 is redundant in protective immunity against most microorganisms other than Mycobacteria and Salmonella. Moreover, IL-12 is redundant for primary immunity to Mycobacteria and Salmonella in many individuals and for secondary immunity to Mycobacteria but not to Salmonella in most

Evaluation of Dendritic Cell-Tumor Cell Hybrid Vaccine Storage

Clinical trials using dendritic cells (DCs) to treat cancer patients have generated promising results in recent years. However, even simple aspects of this therapy are still not well understood, including the storage and distribution of manufactured vaccines. These processes are essential and must be elucidated in order to reduce costs. We evaluated the effects of different storage conditions on vaccine functionality using mixed lymphocyte reaction (MLR). Vaccine storage at 4 degrees C for up to 72 h had no significant effect on vaccine activity. Shipping to distant places is possible, if vaccines are kept at 4 degrees C and used up to 3 days after manufacture date.Genoa Biotechnology, S

Atividades práticas investigativas no jardim de infância: envolvimento da família

Este Relatório Final de Estágio foi desenvolvido no âmbito do Mestrado em Educação Pré-Escolar e Ensino do 1.º Ciclo do Ensino Básico, encontrando-se dividido em duas partes. Na primeira parte é efetuada uma reflexão crítica sobre as práticas desenvolvidas no âmbito das Práticas Ensino Supervisionadas no 1.º Ciclo do Ensino Básico e na Educação Pré-Escolar. Na segunda parte é apresentado o projeto de investigação-ação. O mote para este trabalho foi a questão-problema: “Qual o impacto do envolvimento da família na implementação de atividades práticas no Jardim de infância?”. Após ter sido efetuada uma revisão bibliográfica procedeu-se à realização do estudo num jardim de infância, utilizando como instrumentos o sistema de acompanhamento das crianças, as respostas das crianças e as notas de campo. A análise estatística do estudo pretendia verificar que os níveis de bem-estar e implicação das crianças, aquando da realização de atividades práticas investigativas, se alteram com o envolvimento da família nas mesmas. Os resultados da investigação demonstram que os níveis de bem-estar e implicação são mais elevados aquando do envolvimento da família nas atividades.This Final Internship Report was written in the scope of the Master in Preschool Education and Teaching for the 1st Cycle of Basic Education. The work is divided into two parts. In the first part, a critical reflection is provided on the practices developed under PES for the 1st ECB and the EPE. In the second part, a research-action project is presented. The driving question behind this work is: “What is the impact of family involvement on the implementation of practical activities in the kindergarten?”. Following a literature review, a study was carried out in a kindergarten using the children monitoring system, children's responses and field notes. The statistical analysis of the study aimed at verifying if the level of well-being, and thus the involvement of the children, changed when the family is involved in the practical activities. Research results showed that the level of well-being and involvement are higher when the family is involved in such activities

Autoimmune regulator (AIRE) contributes to Dectin-1-induced TNF-alpha production and complexes with caspase recruitment domain-containing protein 9 (CARD9), spleen tyrosine kinase (Syk), and Dectin-1

Background: Autoimmune polyendocrinopathy-candidiasis-ectodermal dystrophy (APECED) syndrome is a complex immunologic disease caused by mutation of the autoimmune regulator (AIRE) gene. Autoimmunity in patients with APECED syndrome has been shown to result from deficiency of AIRE function in transcriptional regulation of thymic peripheral tissue antigens, which leads to defective T-cell negative selection. Candidal susceptibility in patients with APECED syndrome is thought to result from aberrant adaptive immunity. Objective: To determine whether AIRE could function in anticandidal innate immune signaling, we investigated an extrathymic role for AIRE in the immune recognition of beta-glucan through the Dectin-1 pathway, which is required for defense against Candida species. Methods: Innate immune signaling through the Dectin-1 pathway was assessed in both PBMCs from patients with APECED syndrome and a monocytic cell line. Subcellular localization of AIRE was assessed by using confocal microscopy. Results: PBMCs from patients with APECED syndrome had reduced TNF-alpha responses after Dectin-1 ligation but in part used a Raf-1-mediated pathway to preserve function. In the THP-1 human monocytic cell line, reducing AIRE expression resulted in significantly decreased TNF-a release after Dectin-1 ligation. AIRE formed a transient complex with the known Dectin-1 pathway components phosphorylated spleen tyrosine kinase and caspase recruitment domain-containing protein 9 after receptor ligation and localized with Dectin-1 at the cell membrane. Conclusion: AIRE can participate in the Dectin-1 signaling pathway, indicating a novel extrathymic role for AIRE and a defect that likely contributes to fungal susceptibility in patients with APECED syndrome. (J Allergy Clin Immunol 2012;129:464-72.)Childrens Hospital of PhiladelphiaJeffrey Modell Diagnostic CenterUniversity of PennsylvaniaCoordenacao de Aperfeicoamento de Pessoal de Nivel Superior (Brazil)Fundacao de Amparo a Pesquisa do Estado de Sao Paulo (FAPESP) [09/51747-3, 99/07399-7]Conselho Nacional de Desenvolvimento Cientifico e Tecnologico [501332/2010-3

Encephalopathy Caused by Human Parvovirus B19 Genotype 1 Associated with <i>Haemophilus influenzae</i> Meningitis in a Newborn

Parvovirus B19 infection is associated with a wide range of clinical manifestations, from asymptomatic to severe neurological disorders. Its major clinical symptoms, fever and rash, are common to multiple viruses, and laboratory tests to detect B19 are frequently not available. Thus, the impact of B19 on public health remains unclear. We report the case of a 38-day old girl admitted to São Paulo Clinical Hospital, Brazil, with an initial diagnosis of bacterial meningitis, seizures, and acute hydrocephalus. Antibiotic therapy was maintained for one week after admission and discontinued after negative laboratory results were obtained. Nine days after symptoms onset, a cerebral spinal fluid (CSF) sample revealed persistent pleocytosis. The complete B19 complete genome was subsequently identified in her CSF by a metagenomic next-generation sequencing approach. This report highlights the possible involvement of B19 in the occurrence of acute neurological manifestations and emphasizes that its possible involvement might be better revealed by the use of metagenomic technology to detect viral agents in clinical situations of unknown or uncertain etiology