Navegando por Palavras-chave "autoimunidade"
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- ItemAcesso aberto (Open Access)Caracterização clínica, molecular e imunológica de pacientes com síndrome poliglandular autoimune do tipo 1(Universidade Federal de São Paulo (UNIFESP), 2016-01-27) Weiler, Fernanda Guimarães [UNIFESP]; Castro, Marise Lazaretti [UNIFESP]; Universidade Federal de São Paulo (UNIFESP)Introduction: Autoimmune polyendocrine syndrome type 1 (APS1) is an autosomal recessive disorder defined by the association of at least two of the three major diseases: chronic mucocutaneous candidiasis (CMC), hypoparathyroidism, and autoimmune adrenal insufficiency, however, many other autoimmune components may develop. In most cases, APS1 appears in infancy or childhood. The disease is caused by mutations in the AIRE gene, resulting in defective AIRE protein, which is essential for self-tolerance through thymic expression of peripheral self-proteins, and deletion of autoreactive T cells. In Brazil, however, the characteristics of APS1 patients are still unknown. Objective: To define the clinical profile of Brazilian APS1 patients; to perform mutational analysis of AIRE gene; to investigate genotype/phenotype correlations; to perform functional study of a novel mutation; and to measure specific autoantibodies. Patients and methods: Information about clinical history was evaluated by a questionnaire, and antibodies against interferon type I and interleukins 17A, 17F and 22 were measured in the sera of the patients. Genomic DNA was used to perform sequencing of all 14 exons and exon/intron boundaries of the AIRE gene. For localization analysis by immunofluorescence microscopy, HeLa cells were transfected with wild-type and mutant (c.560C>G) plasmids. Results: Thirteen patients with clinical diagnosis of APS1 were identified and in all cases the disease first appeared during infancy or childhood. Twenty different manifestations have been diagnosed. Besides being the first sign in the majority (77%), CMC was also the most frequent manifestation, present in all patients. Hypoparathyroidism was observed in 69% and adrenal insufficiency was diagnosed in 77%, while the complete triad was present in 54% of the sample. Every patient carried defects in AIRE, and among 10 identified mutations, 4 have never been reported (c.560C>G, c.966C>A, c.1096-2A>G and c.1347C>A). The most frequent mutation was the c.967_979del, which accounted for 36% of the alleles. As in other series, we were unable to identify correlations between phenotype and the detected mutations. Mutational analyses of relatives allowed the identification of APS1 in an asymptomatic child. In transiently transfected cells, the mutant c.560C>G protein was observed as abnormal perinuclear aggregates, which suggested the mutation harmful potential. All 10 confirmed APS1 patients that were tested for anti-interferon type I showed positive results, and we have found that anti-interleukin-17A titers were negatively correlated with number of manifestations in each patient. Thirteen patients suspected of having the syndrome were also investigated; one of them displayed another new mutation of AIRE, which is expected to be deleterious according to in silico simulations. Conclusions: We were able to identify 14 Brazilian patients with APS1, one of them still asymptomatic. In our cohort, CMC was the most prevalent disease, while the most common mutation was c.967_979del. We detected 4 novel mutations, and another mutation likely to be deleterious in a patient suspected of having the syndrome was also reported. Titers of anti-interleukin-17A were negatively correlated with number of manifestations. Screening for AIRE mutations and analysis of specific auto-antibodies are useful tools to establish the diagnosis in initial or atypical situations.
- ItemSomente MetadadadosCaracterização do teste de imunofluorescência indireta em células hep-2 de anticorpos antinúcleo em enfermos não-autoimunes(Universidade Federal de São Paulo (UNIFESP), 2015-08-19) Agustinelli, Renan de Almeida [UNIFESP]; Andrade, Luiz Eduardo Coelho Andrade [UNIFESP]; Universidade Federal de São Paulo (UNIFESP)Objectives: to assess the frequency of antinuclear antibodies (ANA)-HEp-2 test results, the distribution of various immunofluorescence patterns and reaction titers in patients with various non-autoimmune diseases and compare these parameters to those presented by patients with systemic lupus erythematosus (SLE) and healthy individuals. Patients and Methods: cross-sectional observational study in which 588 patients were evaluated and separated into 4 subgroups (152 patients with multiple co-morbidities, 95 patients with neoplasms, 148 with infectious diseases and 163 with psychiatric diseases), 150 patients with SLE and 918 healthy individuals. We considered the ANA-HEp-2 positive in titers higher than 1:80 using commercial slides evaluated by 2 independent examiners. Results: positive ANA-HEp-2 was observed in 102 (18,3%) patients with non-autoimmune disease, in 146 (96%) of patients with SLE and 118 (12,9%) of healthy individuals. No significant differences were found in titers or patterns between the subgroups of patients with non-autoimmune disease. The titers for ANA-HEp-2 in SLE were higher than in patients with non-autoimmune disease, and, when comparing the titers of the non-autoimmune patients with healthy individuals we found titers 1:160 (p < 0,001) and 1:320 (p =0,001) more frequently in the first group and 1:80 in the second group (p <0,001). The nuclear homogenous and nuclear coarse speckled patterns were more frequent in SLE patients (p < 0,001). In the comparison between patients with non-autoimmune disease and healthy individuals we found higher incidences of nuclear dense fine speckled patterns in the second group (p = 0,004). The most common pattern in all groups was the nuclear fine speckled, presenting lower titers in healthy individuals and in patients with non-autoimmune disease (p < 0,001). When comparing the titers of nuclear fine speckled patterns between patients with non-autoimmune disease and in healthy ones we found the titer 1:160 more frequently among the first group (p = 0,003) and 1:80 in the second group (p < 0,001). Conclusion: our results suggest that the pattern and titer of ANA-HEp-2 are useful parameters to differentiate, not only ANA-HEp-2 results in healthy individuals and in SLE patients, but also to distinguish patients with non-autoimmune disease.
- ItemAcesso aberto (Open Access)Interferência por RNA: uma nova alternativa para terapia nas doenças reumáticas(Sociedade Brasileira de Reumatologia, 2010-12-01) França, Natália Regine de [UNIFESP]; Mesquita Júnior, Danilo [UNIFESP]; Lima, Amanda Bandeira [UNIFESP]; Pucci, Fernando Vianna Cabral; Andrade, Luiz Eduardo Coelho [UNIFESP]; Silva, Neusa Pereira da [UNIFESP]; Universidade Federal de São Paulo (UNIFESP); EUROIMMUN; Fleury Medicina Diagnóstica Setor de ImunologiaRNA interference (RNAi) is a post-transcriptional gene silencing mechanism preserved during evolution. This mechanism, recently described, is mediated by small double-stranded RNAs (dsRNAs) that can specifically recognize a target mRNA sequence and mediate its cleavage or translational repression. The use of RNAi as a tool for gene therapy has been extensively studied, especially in viral infections, cancer, inherited genetic disorders, cardiovascular and rheumatic diseases. Together with data from human genome, the knowledge of gene silencing mediated by RNAi could allow a functional determination of virtually any cell expressed gene and its involvement in cellular functioning and homeostasis. Several in vitro and in vivo therapeutic studies with autoimmune disease animal models have been carried out with promising results. The pathways of tolerance breakage and inflammation are potential targets for RNAi therapy in inflammatory autoimmune diseases. This review will present the basic principles of RNAi and discuss several aspects of RNAi-based therapeutic approaches, from in vitro tool design and target identification to in vivo pre-clinical drug delivery, and tests of autoimmune diseases in human cells and animal models. Finally, this review will present some recent clinical experience with RNAi-based therapy
- ItemSomente MetadadadosSistema hla de classe ii modula a relação entre infecção viral e autoimunidade em famílias com diabetes melito do tipo 1 múltiplo(Universidade Federal de São Paulo (UNIFESP), 2015-12-16) Bergamin, Carla Sanchez [UNIFESP]; Dib, Sergio Atala Dib [UNIFESP]; Universidade Federal de São Paulo (UNIFESP)Article 1 A complex interaction of genetic and environmental factors can trigger the immune-mediated mechanism responsible for type 1 diabetes mellitus (T1DM) establishment. The role of environmental factors in this process has been exhaustive studied and viruses are among the most probable ones, especially enteroviruses. Improvements in enterovirus detection methods and randomized studies with patient follow-up have confirmed the importance of these viruses in the pathogenesis of T1DM. However the frequency of viruses induces autoimmunity or ? beta cell destruction and the mechanisms and pathways how they increment the autoimmunity in T1DM still to be determined. Here, we review these mechanisms and all evolution in enterovirus studies and T1DM. Advances in molecular and genomic studies may facilitate the identification of pathways at earlier stages of autoimmunity when preventive and therapeutic approaches may be more effective. Article 2 The mechanisms and pathways which enterovirus leads to autoimmunity and ?-cell destruction in T1D involve a complex interaction among virus, innate immunity response (toll like system) and islet-? cell autoimmunity. The current study evaluates this relation in T1D multiplex-sibs families. Forty long-term duration T1D patients and 11 T1D non-affected siblings (T1DNAS) from T1D multiplex families and 54 normal control (NC) subjects were studied. Prevalence of Coxsackievirus B (CBV1, CBV3, CBV4, CBV5, CBV6) and three echovirus E6, E7 and E30 serotypes were similar among NC, T1D and T1DNAS except for CVB2 antibodies that were more prevalent in T1DNAS. TLR4 expression was higher in T1D multiplex families individuals than in NC subjects and there were positive correlation between TLR2/TLR4 with CBV2 antibodies (rS: 0.45; P=0.03), with sera concentration of CXCL8 (rS: 0.65, P=0.002) and with TNF-? (rS: 0.5, P=0.01) in both T1D patients and T1DNAS. There was a concordant correlation between HLA genotype risk to T1D and IA-2A positivity (OR: 38.8; P=0.021). HLA protective haplotypes to T1D prevalence was higher in T1DNAS than in his/her affected siblings in these T1D multiplex families. These data suggest mechanisms how HLA genetic background could influence the relationship among viral infection, innate immunity and anti-pancreatic islet autoimmunity.
- ItemAcesso aberto (Open Access)Sistema imunitário - parte II: fundamentos da resposta imunológica mediada por linfócitos T e B(Sociedade Brasileira de Reumatologia, 2010-10-01) Mesquita Júnior, Danilo [UNIFESP]; Araújo, Júlio Antônio Pereira; Catelan, Tânia Tieko Takao [UNIFESP]; Souza, Alexandre Wagner Silva de [UNIFESP]; Cruvinel, Wilson de Melo [UNIFESP]; Andrade, Luiz Eduardo Coelho [UNIFESP]; Silva, Neusa Pereira da [UNIFESP]; Universidade Federal de São Paulo (UNIFESP)The immune system consists of an intricate network of organs, cells, and molecules responsible for maintaining the body's homeostasis and responding to aggression in general. Innate immunity operates in conjunction with adaptive immunity and is characterized by rapid response to aggression, regardless of previous stimulus, being the organism first line of defense. Its mechanisms include physical, chemical and biological barriers, cellular components, as well as soluble molecules. The organism first line of defense against tissue damage involves several steps closely integrated and constituted by different components of this system. The aim of this review is to restore the foundations of this response, which has high complexity and consists of several components that converge to articulate the development of adaptive immune response. We selected some of the following steps to review: perception and molecular recognition of aggressive agents; activation of intracellular pathways, which result in vascular and tissue changes; production of a myriad of mediators with local and systemic effects on cell activation and proliferation, synthesis of new products involved in the chemoattraction and migration of cells specialized in destruction and removal of offending agent; and finally, tissue recovery with restoration of functional tissue or organ.
- ItemAcesso aberto (Open Access)Sistema imunitário: Parte I. Fundamentos da imunidade inata com ênfase nos mecanismos moleculares e celulares da resposta inflamatória(Sociedade Brasileira de Reumatologia, 2010-08-01) Cruvinel, Wilson de Melo [UNIFESP]; Mesquita Júnior, Danilo [UNIFESP]; Araújo, Júlio Antônio Pereira; Catelan, Tânia Tieko Takao [UNIFESP]; Souza, Alexandre Wagner Silva de [UNIFESP]; Silva, Neusa Pereira da [UNIFESP]; Andrade, Luiz Eduardo Coelho [UNIFESP]; Universidade Federal de São Paulo (UNIFESP); Pontifícia Universidade Católica de Goiás cursos de Medicina e BiomedicinaThe immune system consists of an intricate network of organs, cells, and molecules responsible for maintaining the body's homeostasis and responding to aggression in general. Innate immunity operates in conjunction with adaptive immunity and is characterized by rapid response to aggression, regardless of previous stimulus, being the organism first line of defense. Its mechanisms include physical, chemical and biological barriers, cellular components, as well as soluble molecules. The organism first line of defense against tissue damage involves several steps closely integrated and constituted by different components of this system. The aim of this review is to restore the foundations of this response, which has high complexity and consists of several components that converge to articulate the development of adaptive immune response. We selected some of the following steps to review: perception and molecular recognition of aggressive agents; activation of intracellular pathways, which result in vascular and tissue changes; production of a myriad of mediators with local and systemic effects on cell activation and proliferation, synthesis of new products involved in the chemoattraction and migration of cells specialized in destruction and removal of offending agent; and finally, tissue recovery with restoration of functional tissue or organ.
- ItemAcesso aberto (Open Access)Sistema imunitário: parte III. O delicado equilíbrio do sistema imunológico entre os pólos de tolerância e autoimunidade(Sociedade Brasileira de Reumatologia, 2010-12-01) Souza, Alexandre Wagner Silva de [UNIFESP]; Mesquita Júnior, Danilo [UNIFESP]; Araújo, Júlio Antônio Pereira; Catelan, Tânia Tieko Takao [UNIFESP]; Cruvinel, Wilson de Melo [UNIFESP]; Andrade, Luiz Eduardo Coelho [UNIFESP]; Silva, Neusa Pereira da [UNIFESP]; Universidade Federal de São Paulo (UNIFESP); Pontifícia Universidade Católica de Goiás cursos de Medicina e BiomedicinaThe immune system consists of an intricate network of organs, cells, and molecules responsible for maintaining the body's homeostasis and responding to aggression in general. Innate immunity operates in conjunction with adaptive immunity and is characterized by rapid response to aggression, regardless of previous stimulus, being the organism first line of defense. Its mechanisms include physical, chemical and biological barriers, cellular components, as well as soluble molecules. The organism first line of defense against tissue damage involves several steps closely integrated and constituted by different components of this system. The aim of this review is to restore the foundations of this response, which has high complexity and consists of several components that converge to articulate the development of adaptive immune response. We selected some of the following steps to review: perception and molecular recognition of aggressive agents; activation of intracellular pathways, which result in vascular and tissue changes; production of a myriad of mediators with local and systemic effects on cell activation and proliferation, synthesis of new products involved in the chemoattraction and migration of cells specialized in destruction and removal of offending agent; and finally, tissue recovery with restoration of functional tissue or organ