RESUMEN
The integrins, a family of cell surface proteins, mediate cell adhesion and may influence within the intestinal mucosa processes such as migration and/or proliferation and differentiation of enterocytes and lymphocytes. The aim of this study was to examine the distribution pattern of integrin subunits (VLA alpha1, alpha2, alpha3, alpha4, alpha5, alpha6, beta1 chains) in normal intestinal mucosa and in that of patients with active coeliac disease (CD) and CD in remission. Immunohistochemical techniques and double immunostainings with monoclonal antibodies were used for investigation of the VLA alpha family of integrins and beta1 chain distribution. While the majority of the findings are consistent with the few data previously reported in the literature, surprising is the finding of a lack of expression of VLAalpha1 on the intraepithelial lymphocytes in the coeliac mucosa. The deficient VLA alpha1 expression on IEL in coeliac but not in normal mucosa may imply a genetic variation or a specific deficiency of gene expression during T cell differentiation and activation.
Asunto(s)
Enfermedad Celíaca/metabolismo , Mucosa Intestinal/metabolismo , Receptores de Antígeno muy Tardío/metabolismo , Anticuerpos Monoclonales , Niño , Preescolar , Citometría de Flujo , Técnica del Anticuerpo Fluorescente , Humanos , InmunohistoquímicaRESUMEN
The incidence of coeliac disease is different throughout Europe. The aim of our study was to investigate its true prevalence using antigliadin and endomysial antibodies in 4615 healthy adults within two different population groups in Northern Italy: 140 were positive for antigliadin antibodies (AGA), 111 only for AGA IgG, 17 for AGA IgA and 12 for IgG and IgA. Of those positive for AGA, nine had an abnormal small-intestine mucosa and were positive for endomysium antibodies (EmA) using the umbilical cord test, a novel methodology. The prevalence, 163/100,000 in the Italian group and 216/100,000 in the German group, is much higher than what was assumed. The positive predictive value of the EmA, confirmed by biopsy, is 100%, that of AGA IgG 2%, of AGA IgA 12% and of the combined AGA IgA and IgG 33%. AGA positive but EmA negative patients displayed normal histological features and distributions of alpha/beta and gamma/delta T-cell receptors on intraepithelial lymphocytes. We can therefore conclude that antigliadin antibodies are not an ideal tool for screening purposes; the umbilical cord EmA test is superior owing to its optimal sensitivity, specificity, high positive predictive value and low cost.
Asunto(s)
Enfermedad Celíaca/diagnóstico , Enfermedad Celíaca/epidemiología , Tamizaje Masivo/métodos , Adolescente , Adulto , Anciano , Anciano de 80 o más Años , Anticuerpos/sangre , Autoinmunidad , Biomarcadores/sangre , Enfermedad Celíaca/etnología , Enfermedad Celíaca/inmunología , Femenino , Técnica del Anticuerpo Fluorescente Indirecta/métodos , Alemania/etnología , Gliadina/inmunología , Humanos , Inmunoglobulina A/sangre , Inmunoglobulina A/inmunología , Inmunoglobulina G/sangre , Inmunoglobulina G/inmunología , Italia/epidemiología , Yeyuno/inmunología , Yeyuno/patología , Recuento de Linfocitos , Masculino , Persona de Mediana Edad , Músculo Liso/inmunología , Valor Predictivo de las Pruebas , Prevalencia , Receptores de Antígenos de Linfocitos T , Muestreo , Sensibilidad y Especificidad , Pruebas Serológicas/métodos , Cordón Umbilical/inmunologíaRESUMEN
The binding patterns of gliadin and selected lectins to jejunal biopsy specimens obtained from children with total villous atrophy during active celiac disease (CD; 19 patients) and in remission (16 patients) were examined by light microscopy. Three categories of carbohydrate-specific lectins were chosen for the study: those recognizing mannose/glucose residues, those recognizing N-acetyl-glucosamine/glucose (glcNAc/glc) residues, and those recognizing N-acetylgalactosamine/galactose (galNAc/gal) residues. The galNAc/gal lectins, with the exception of phaseolus vulgaris agglutinin variants, presented a typical staining of the luminal surface of the jejunal mucosa obtained from CD patients. However, these lectins displayed no reactivity to jejunal sections of CD patients in remission or control biopsies that included healthy children (25 children) and patients suffering from cow milk protein allergy (10 children). The glcNAc/glc lectin showed a strong preferential recognition of CD jejunal tissue but also bound with less intensity to specimens from patients with cow milk allergies and healthy children. Unlike other galNAc/gal lectins, phaseolus vulgaris agglutinin variants were indistinguishable in their binding patterns to the mucosa of control groups and CD patients in remission and failed to react to CD biopsies. The mannose/glc lectins were not distinctive in their binding patterns. In all cases, lectin binding was specifically inhibited by the lectins' competitive saccharides. Atypical of lectin binding patterns, gliadin reactivity was restricted to intracellular areas of enterocytes and was unique to active CD mucosa. The distinctive binding patterns of lectins and gliadin provide a diagnostic tool to distinguish patients with active CD from those in remission or patients with other intestinal disorders.(ABSTRACT TRUNCATED AT 250 WORDS)
Asunto(s)
Enfermedad Celíaca/metabolismo , Gliadina/metabolismo , Mucosa Intestinal/metabolismo , Lectinas/metabolismo , Unión Competitiva/fisiología , Biopsia , Enfermedad Celíaca/patología , Niño , Preescolar , Femenino , Humanos , Inmunoglobulina A/análisis , Inmunoglobulina G/análisis , Inmunoglobulina M/análisis , Inmunohistoquímica , Lactante , Mucosa Intestinal/patología , Masculino , Unión Proteica , Valores de Referencia , Inducción de RemisiónRESUMEN
The ultra structural binding sites of endomysium antibodies have been studied on human umbilical cord tissue. The sensitivity and specificity of IgA endomysium antibodies were compared with recently described methods using basement membrane of smooth muscle of monkey oesophagus. Thirty adults affected by coeliac disease (10 in remission) and 75 healthy adult controls with normal intestinal mucosa (35 false antigliadin positive) were investigated. Sensitivity and correlation of endomysium antibodies with total villous atrophy in untreated coeliac disease patients were 100% on the human umbilical cord smooth muscles, and only 90% on the muscular layer of primate oesophagus. Indirect immunofluorescence was superior to peroxidase staining in detecting these IgA antibodies. The easy availability and enhanced testing sensitivity of the umbilical cord is an advance towards a better diagnostic tool for coeliac disease.