282 research outputs found
Narcolepsy as an autoimmune disease: the role of H1N1 infection and vaccination.
No full textNarcolepsy is a sleep disorder characterised by loss of hypothalamic hypocretin (orexin) neurons. The prevalence of narcolepsy is about 30 per 100 000 people, and typical age at onset is 12-16 years. Narcolepsy is strongly associated with the HLA-DQB1*06:02 genotype, and has been thought of as an immune-mediated disease. Other risk genes, such as T-cell-receptor α chain and purinergic receptor subtype 2Y11, are also implicated. Interest in narcolepsy has increased since the epidemiological observations that H1N1 infection and vaccination are potential triggering factors, and an increase in the incidence of narcolepsy after the pandemic AS03 adjuvanted H1N1 vaccination in 2010 from Sweden and Finland supports the immune-mediated pathogenesis. Epidemiological observations from studies in China also suggest a role for H1N1 virus infections as a trigger for narcolepsy. Although the pathological mechanisms are unknown, an H1N1 virus-derived antigen might be the trigger
Autoantibodies against ganglioside GM3 are associated with narcolepsy-cataplexy developing after Pandemrix vaccination against 2009 pandemic H1N1 type influenza virus
No full textFollowing the mass vaccinations against pandemic influenza A/H1N1 virus in 2009, a sudden increase in juvenile onset narcolepsy with cataplexy (NC) was detected in several European countries where AS03-adjuvanted Pandemrix vaccine had been used. NC is a chronic neurological disorder characterized by excessive daytime sleepiness and cataplexy. In human NC, the hypocretin-producing neurons in the hypothalamus or the hypocretin signaling pathway are destroyed by an autoimmune reaction. Both genetic (e.g. HLA-DQB1*0602) and environmental risk factors (e.g. Pandemrix) contribute to the disease development, but the underlying and the mediating immunological mechanisms are largely unknown. Influenza virus hemagglutinin is known to bind gangliosides, which serve as host cell virus receptors. Anti-ganglioside antibodies have previously been linked to various neurological disorders, like the Guillain-Barré syndrome which may develop after infection or vaccination. Because of these links we screened sera of NC patients and controls for IgG anti-ganglioside antibodies against 11 human brain gangliosides (GM1, GM2, GM3, GM4, GD1a, GD1b, GD2, GD3, GT1a, GT1b, GQ1b) and a sulfatide by using a line blot assay. Samples from 173 children and adolescents were analyzed: 48 with Pandemrix-associated NC, 20 with NC without Pandemrix association, 57 Pandemrix-vaccinated and 48 unvaccinated healthy children. We found that patients with Pandemrix-associated NC had more frequently (14.6%) anti-GM3 antibodies than vaccinated healthy controls (3.5%) (P = 0.047). Anti-GM3 antibodies were significantly associated with HLA-DQB1*0602 (P = 0.016) both in vaccinated NC patients and controls. In general, anti-ganglioside antibodies were more frequent in vaccinated (18.1%) than in unvaccinated (7.3%) individuals (P = 0.035). Our data suggest that autoimmunity against GM3 is a feature of Pandemrix-associated NC and that autoantibodies against gangliosides were induced by Pandemrix vaccination
Is it dietary insulin?
No full textIn humans the primary trigger of insulin-specific immunity is a modified self-antigen, that is, dietary bovine insulin, which breaks neonatal tolerance to self-insulin. The immune response induced by bovine insulin spreads to react with human insulin. This primary immune response induced in the gut immune system is regulated by the mechanisms of oral tolerance. Genetic factors and environmental factors, such as the gut microflora, breast milk-derived factors, and enteral infections, control the development of oral tolerance. The age of host modifies the immune response to oral antigens because the permeability of the gut decreases with age and mucosal immune response, such as IgA response, develops with age. The factors that control the function of the gut immune system may either be protective from autoimmunity by supporting tolerance, or they may induce autoimmunity by abating tolerance to dietary insulin. There is accumulating evidence that the intestinal immune system is aberrant in children with type I diabetes (T1D). Intestinal immune activation and increased gut permeability are associated with T1D. These aberrancies may be responsible for the impaired control of tolerance to dietary insulin. Later in life, factors that activate insulin-specific immune cells derived from the gut may switch the response toward cytotoxic immunity. Viruses, which infect P cells, may release autoantigens and potentiate their presentation by an infection-associated "danger signal." This kind of secondary immunization may cause functional changes in the dietary insulin primed immune cells, and lead to the infiltration of insulin-reactive T cells to the pancreatic islets.</p
Avaliação cardiovascular subclínica, metabólica e nutricional de crianças e adolescentes com doença celíaca em tratamento
No full textTese (doutorado) - Universidade Federal de Santa Catarina, Centro de Ciências da Saúde, Programa de Pós-Graduação em Ciências Médicas, Florianópolis, 2015.A doença celíaca (DC) é uma condição crônica, a qual perdura por toda a vida. O impacto da dieta isenta de glúten em aspectos nutricionais e em outros parâmetros bioquímicos e subclínicos têm sido sistematicamente investigado, mas novos estudos ainda são necessários. Os objetivos deste estudo foram avaliar características cardiovasculares subclínicas, metabólicas e nutricionais em crianças e adolescentes portadores de DC em tratamento ambulatorial, por meio de aspectos demográficos, laboratoriais, ultrassonográficos e ecocardiográficos, bem como verificar associações destas variáveis de um grupo com DC com um grupo semelhante mas saudável. Realizou-se um estudo observacional, transversal e prospectivo, com amostras pareadas por sexo, idade e estado nutricional, de 30 participantes com DC e 30 controles saudáveis. Foram avaliados lipídios, hematócrito, hemoglobina, anticorpo anti-gliadina IgA, proteína C reativa de alta sensibilidade e as citocinas IL-1ß, IL-1ra, IL-2, IL-4, Il-6, Il-10, Il-17, interferon gama e fator de necrose tumoral alfa. Foram medidas a espessura médio-intimal da carótida comum direita por meio de ultrassom, e as dimensões das cavidades esquerdas e as funções do ventrículo esquerdo por ecocardiografia. Para a análise estatística utilizou-se o Teste-t e testes exploratórios de análise multivariada, com nível de significância alfa de 0,05 quando aplicável. Verificou-se níveis do colesterol total e do LDL-colesterol mais altos no grupo DC (pvalor=0,0268 e 0,0253 respectivamente) e do HDL-c abaixo do normal em ambos os grupos; a espessura médio-intimal da carótida comum direita aumentada com maior frequência no grupo DC (pvalor=0,0049); não houve disfunções ventriculares em ambos os grupos. Concluiu-se, então que crianças e adolescentes com DC, em dieta isenta de glúten por pelo menos um ano, quando comparados com um grupo saudável, semelhante em termos de sexo, idade e estado nutricional, apresentam dislipidemia, fator de risco cardiovascular, e a EMIC aumentada, indicativo de aterosclerose subclínica. Mostram também marcadores pró e anti-inflamatórios com um padrão que sugere que, mesmo sem glúten, o organismo parece manter estes mecanismos.incipientemente ativos.Abstract : Celiac disease (CD) is a chronic condition, which lasts for a lifetime. The impact of a gluten-free diet on nutritional and other biochemical and subclinical parameters and have been systematically investigated, but further studies are still needed. The objectives of this study were to evaluate subclinical cardiovascular, nutritional and metabolic characteristics in children and adolescents with CD in outpatient treatment, by demographics, laboratory, ultrasound and echocardiography, and to verify associations of these variables of a group of DC with a similar healthy group. We conducted an observational, cross-sectional and prospective study, with samples paired by sex, age and nutritional status with 30 participants with CDand 30 controls. Serum lipids, hematocrit, hemoglobin, IgA anti-gliadin antibody, high sensitive C-reactive protein, serum interleukyns IL-1ß, IL-1ra, IL-2, IL-4, IL-6, IL-10, IL-17 , gamma interferon and alpha tumor necrosis factor. We measured the intima-media thickness of the common carotid through high resolution digital linear ultrasound, and the dimensions of the left cavities and left ventricular functions by echocardiography. For statistical analysis we used the t-test and exploratory multivariate analysis testing, with alpha significance level of 0.05 when applicable. There was total cholesterol and LDL-cholesterol levels higher in CD group (pvalue = 0.0268 and 0.0253 respectively) and HDL-cholesterol below normal levels in both groups; the media-intima thickness of the right common carotid artery (cMIT) was more frequently increased in those with CD (pvalue = 0.0049); and lack of ventricular dysfunction in both groups. It was concluded then that children and adolescents with CD on a gluten-free diet for at least one year, compared with a healthy group, similar in terms of gender, age and nutritional status, have dyslipidemia, a cardiovascular risk factor, and increased, cMIT indicative of subclinical atherosclerosis. They also have pro- and anti-inflammatory markers with a pattern that suggests that even without gluten, the body seems to keep assets and incipients these mechanisms
- …
