RESUMO
AIM: Anti-Saccharomyces cerevisiae antibodies (ASCA), anti-nuclear associated anti-neutrophil antibodies (NANA) and antibodies to exocrine pancreas (PAB), are serological tools for discriminating Crohn's disease (CrD) and ulcerative colitis (UC). Like CrD, coeliac disease (CoD) is an inflammatory bowel disease (IBD) associated with (auto) antibodies. Performing a multicenter study we primarily aimed to determine the performance of ASCA, NANA and PAB tests for IBD diagnosis in children and adults, and secondarily to evaluate the prevalence of these markers in CoD. METHODS: Sera of 109 patients with CrD, 78 with UC, 45 with CoD and 50 healthy blood donors were retrospectively included. ASCA, NANA and PAB were detected by indirect immunofluorescence (IIF). RESULTS: ASCA+/NANA- profile displayed a positive predictive value of 94.2% for CrD. Detection of ASCA was correlated with a more severe clinical profile of CrD and treatment of the disease did not influence their serum levels. ASCA positivity was found in 37.9% of active CoD. PAB were found in 36.7% CrD and 13.3% CoD patients and were not correlated with clinical features of CrD, except with an early onset of the disease. Fifteen CrD patients were ASCA negative and PAB positive. CONCLUSION: ASCA and PAB detected by IIF are specific markers for CrD although their presence does not rule out a possible active CoD. The combination of ASCA, NANA and PAB tests improves the sensitivity of immunological markers for CrD. Repeating ASCA, NANA, and PAB testing during the course of CrD has no clinical value.
Assuntos
Anticorpos Anticitoplasma de Neutrófilos/sangue , Anticorpos Antinucleares/sangue , Anticorpos Antifúngicos/sangue , Doenças Inflamatórias Intestinais/sangue , Doenças Inflamatórias Intestinais/imunologia , Pâncreas Exócrino/imunologia , Saccharomyces cerevisiae/imunologia , Adolescente , Adulto , Idoso , Biomarcadores/sangue , Doença Celíaca/sangue , Doença Celíaca/diagnóstico , Doença Celíaca/imunologia , Criança , Doença Crônica , Estudos de Coortes , Colite Ulcerativa/sangue , Colite Ulcerativa/diagnóstico , Colite Ulcerativa/imunologia , Doença de Crohn/sangue , Doença de Crohn/diagnóstico , Doença de Crohn/imunologia , Estudos Transversais , Diagnóstico Diferencial , Feminino , Técnica Indireta de Fluorescência para Anticorpo/métodos , Humanos , Doenças Inflamatórias Intestinais/diagnóstico , Masculino , Pessoa de Meia-Idade , Estudos Retrospectivos , Sensibilidade e EspecificidadeRESUMO
According to one of the theories formulated to explain the etiology of Alzheimer's disease (AD), amylosis may reflect a specific inflammatory response. Two inflammatory proteins, lithostathine and PAP, were evidenced by immunohistochemistry in senile plaques and neurofibrillary tangles of patients with AD. In addition, lithostathine and PAP were significantly increased in the cerebrospinal fluid of patients with AD when compared to patients with multiple sclerosis, another inflammatory disease, and to normal control subjects. However, no correlation was observed with age of occurrence. Furthermore, lithostathine and PAP were increased even at the very early stages of AD, and their level remained elevated during the course of the AD unlike TNFalpha whose level, very high at very early stages, regularly decreased. Finally, if part of lithostathine and PAP are synthesized in the brain, a large part comes from serum by passage over the blood-brain barrier. These results indicate (i) the existence of an acute phase response followed by a chronic inflammation in AD, and (ii) that lithostathine and PAP are involved even at the first pre-clinical biochemical events of AD. In addition, because lithostathine undergoes an autolytic cleavage leading to its precipitation and the formation of fibrils, we believe that it may be involved in amyloidosis and tangles by allowing heterogeneous precipitation of other proteins.
Assuntos
Proteínas de Fase Aguda/líquido cefalorraquidiano , Doença de Alzheimer/líquido cefalorraquidiano , Antígenos de Neoplasias , Biomarcadores Tumorais , Proteínas de Ligação ao Cálcio/líquido cefalorraquidiano , Lectinas Tipo C , Proteínas do Tecido Nervoso , Emaranhados Neurofibrilares/metabolismo , Placa Amiloide/metabolismo , Adulto , Idoso , Idoso de 80 Anos ou mais , Doença de Alzheimer/sangue , Proteínas de Ligação ao Cálcio/sangue , Distribuição de Qui-Quadrado , Citocinas/líquido cefalorraquidiano , Humanos , Litostatina , Pessoa de Meia-Idade , Esclerose Múltipla/sangue , Esclerose Múltipla/líquido cefalorraquidiano , Proteínas Associadas a Pancreatite , Lobo Parietal/metabolismo , Lobo Parietal/patologia , Estatísticas não ParamétricasRESUMO
Large polysaccharide molecules composing the glycocalyx have been shown to prevent cell adhesion. However, this process was not observed microscopically. Terbium labeling, combined with a new quantitative imaging method based on electron energy loss spectroscopy, allowed specific glycocalyx staining with excellent contrast. Image analysis enabled us to compare glycocalyx structure in free membrane areas and contacts between monocytic cells and bound erythrocytes. Apparent glycocalyx thickness, in contact areas, was half of the sum of glycocalyx thicknesses in free areas without label density increase. Ultrastructural immunogold localization of CD43 molecules, a major component of glycocalyx, was also demonstrated to be excluded from contact areas during adhesion. Thus, both approaches strongly suggest that some glycocalyx elements must exit from contact to allow binding of adhesion molecules.
Assuntos
Antígenos CD , Glicocálix/fisiologia , Adesão Celular , Células Cultivadas/ultraestrutura , Glicocálix/química , Glicocálix/ultraestrutura , Humanos , Leucossialina , Microscopia Eletrônica , Sialoglicoproteínas/análise , Sialoglicoproteínas/metabolismo , TérbioRESUMO
PURPOSE: Anti-tissue transglutaminase antibodies (ATTG) have helped to distinguish atypical and silent clinical forms of celiac disease (CD). Immunological diagnosis or follow-up of the disease is now based in France in first line upon IgA ATTG serum evaluation. In the University Hospital of Marseille, the serological diagnosis of CD had consisted during several years in simultaneous determination of both IgA anti-endomysial antibodies (AEA) and IgA ATTG. In literature, few studies focused on the concordance between the two tests and a very few epidemiological data about CD in France are available. METHODS: Five thousand nine hundred and eighty-one patients for whom both AEA and ATTG testing were available were retrospectively included. Characteristics of this cohort were detailed. We numbered and analyzed especially bioclinical charts from patients with AAE/AATG discordance. RESULTS: Among our patients, all ages and all medical subspecialties were represented. Eighty-five new cases of CD were identified. Among the 6516 serum evaluations performed, only 31 tests were discordant. CONCLUSIONS: Our data give information about CD epidemiology in France. They support the contention that ATTG have to be evaluated in first line for CD diagnosis.
Assuntos
Autoanticorpos/sangue , Doença Celíaca/diagnóstico , Continuidade da Assistência ao Paciente , Programas de Rastreamento/métodos , Adolescente , Adulto , Idoso , Idoso de 80 Anos ou mais , Doença Celíaca/sangue , Doença Celíaca/epidemiologia , Criança , Pré-Escolar , Continuidade da Assistência ao Paciente/estatística & dados numéricos , Feminino , França/epidemiologia , Hospitais Universitários/estatística & dados numéricos , Humanos , Lactente , Recém-Nascido , Masculino , Pessoa de Meia-Idade , Adulto JovemRESUMO
Astrocytes exert many active roles in brain homeostasis, potentially including the regulation of immune reactions. They possess a substantial aptitude for plasticity and, indeed, functional and phenotypic changes are frequently encountered in reactive gliosis observed in brain injuries. The significance of reactive astrocytes is still poorly defined, but it is clear that these cells are an important source of cytokines in inflamed brain. How tumor necrosis factor (TNF) and TNF-receptor family members contribute to this reaction is an interesting issue that is currently being explored. It was previously shown that reactive astrocytes express high levels of Fas (CD95) and respond to Fas ligand (CD95L) by apoptosis or IL-8 production. TWEAK (Apo-3 ligand) is a recently identified member of the TNF family that is produced mainly by leukocytes that can infiltrate the inflamed brain and thus influence astrocyte behavior. Here we show that human astrocytes derived from different regions of the brain specifically bind TWEAK and are totally resistant to TWEAK mediated apoptosis. In addition, high amounts of IL-8 and IL-6 were secreted by astrocytes after TWEAK exposure. Finally, expression of cell surface molecules involved in the propagation and/or maintenance of brain inflammation was determined. TWEAK significantly increased ICAM-1 expression on astrocytes, whereas no modification was detected in the expression of Fas, TNFRI, B7-1, or MHC molecules. In conclusion, the proinflammatory effects induced by TWEAK on astrocytes in culture recapitulate many characteristics of reactive astrocytes observed in vivo, suggesting that TWEAK could play a significant role in brain inflammation.
Assuntos
Astrócitos/efeitos dos fármacos , Astrócitos/metabolismo , Encéfalo/fisiopatologia , Proteínas de Transporte/metabolismo , Proteínas de Transporte/farmacologia , Encefalite/metabolismo , Encefalite/fisiopatologia , Proteínas Reguladoras de Apoptose , Astrócitos/citologia , Encéfalo/efeitos dos fármacos , Encéfalo/patologia , Citocina TWEAK , Encefalite/patologia , Feto , Gliose/metabolismo , Gliose/patologia , Gliose/fisiopatologia , Humanos , Molécula 1 de Adesão Intercelular/efeitos dos fármacos , Molécula 1 de Adesão Intercelular/metabolismo , Interleucina-6/metabolismo , Interleucina-8/metabolismo , Rombencéfalo/citologia , Rombencéfalo/efeitos dos fármacos , Rombencéfalo/metabolismo , Fator de Necrose Tumoral alfa/metabolismo , Fatores de Necrose TumoralRESUMO
Astrocytes are a major cellular component of the brain that are capable of intense proliferation and metabolic activity during diverse inflammatory brain diseases (such as multiple sclerosis, Alzheimer's dementia, tumor, HIV encephalitis, or prion disease). In this biological process, called reactive gliosis, astrocyte apoptosis is frequently observed and could be an important mechanism of regulation. However, the factors responsible for apoptosis in human astrocytes are poorly defined. Here, we report that short term cultured astrocytes derived from different brain regions express significant levels of CD95 at their surface. Only late passage astrocytes are sensitive to CD95 ligation using either CD95 mAb or recombinant CD95 ligand. Blocking experiments using caspase inhibitors with different specificities (DEVD-CHO, z-VAD-fmk, and YVAD-cmk), an enzymatic activity assay, and immunoblotting show that CPP32/caspase-3 play a prominent role in CD95-induced astrocyte death. In contrast, early passage astrocytes are totally resistant to death, but a significant increase in astrocytic IL-8 secretion (p < 0.001, by Wilcoxon's test for paired samples) is observed after CD95 triggering. Production of IL-8 contributes to the resistance of astrocytes to CD95 ligation. Furthermore, in the presence of IFN-gamma, resistant astrocytes became sensitive to CD95-mediated death. These data suggest that microenvironmental factors can influence the consequences of CD95 ligation on astrocytes. Therefore, we propose that CD95 expressed by human astrocytes plays a pivotal role in the regulation of astrocyte life and death and may be a key factor in inflammatory processes in the brain, such as reactive gliosis.