Irritable bowel syndrome in celiac disease - relationships to celiac disease antibodies and levels of pro-inflammatory cytokines / Síndrome del intestino irritable en la enfermedad celíaca: relaciones con los anticuerpos contra la enfermedad celíaca y los niveles de citocinas proinflamatorias

ABSTRACT Background: Evidence indicates that low-grade inflammation can alter gastrointestinal motor and sensory function and might contribute to the genesis of symptoms in IBS. Objective: To examine relationships between IBS, disease antibodies and cytokine titers in celiac patients and a control group. Materials and methods: IBS, CD activity and serum levels of IL-6, IL-8 and IL12/23p40 were determined in celiac patients and controls. Results: 123 celiac patients were included, 89% were female. 59% demonstrated disease activity and 32% met IBS criteria. Prevalence of IBS was not different between patients who adhered or did not adhere to GFD as well as between patients with or without positive antibodies. Celiac patients had increased levels of IL-6, IL-8 and IL12/23p40 as compared to controls. Higher levels of cytokines were found in celiac patients with IBS than in those without IBS. No difference in levels of cytokines was found between patients with and without CD positive antibodies. A significant negative correlation between the mental component of QoL and IL-6 and IL12/23p40 levels was found, but not with IL-8. Conclusion: Higher levels of inflammatory cytokines were found in CD patients with IBS than in either those without IBS or controls, indicating that IBS symptoms are associated with an increase in the inflammatory response and a decrease in quality of life of CD patients. These differences in cytokine levels were not related to CD antibodies status suggesting that IBS, in CD, is related to a different inflammatory process than that which is relevant to CD.

RESUMEN Antecedentes: la evidencia indica que la inflamación de bajo grado puede alterar la función motora y sensorial gastrointestinal y puede contribuir a la aparición de síntomas en el SII. Objetivo: Examinar la relación entre SII, anticuerpos contra enfermedades y títulos de citocinas en pacientes celíacos y un grupo de control. Materiales y métodos: se determinaron los síntomas de SII, actividad de CD y niveles séricos de IL-6, IL-8 e IL12 / 23p40 en pacientes celíacos y controles. Resultados: se incluyeron 123 pacientes celíacos, el 89% eran mujeres. El 59% demostró actividad de la enfermedad y el 32% cumplió con los criterios del SII. La prevalencia del SII no fue diferente entre los pacientes que se adhirieron o no se adhirieron a GFD, así como entre los pacientes con o sin anticuerpos positivos. Los pacientes celíacos tenían niveles aumentados de IL-6, IL-8 e IL12 / 23p40 en comparación con los controles. Se encontraron niveles más altos de citocinas en pacientes celíacos con SII que en aquellos sin SII. No se encontraron diferencias en los niveles de citocinas entre pacientes con y sin anticuerpos CD positivos. Se encontró una correlación negativa significativa entre el componente mental de la calidad de vida y los niveles de IL-6 e IL12 / 23p40, pero no con IL-8. Conclusión: Se encontraron niveles más altos de citocinas inflamatorias en pacientes con EC con SII que en aquellos sin SII o controles, lo que indica que los síntomas del SII están asociados con un aumento en la respuesta inflamatoria y una disminución en la calidad de vida de los pacientes con CD. Estas diferencias en los niveles de citocinas no estaban relacionadas con el estado de los anticuerpos contra la CD, lo que sugiere que el SII, en la CD, está relacionado con un proceso inflamatorio diferente al que es relevante para la CD.

Prevalence of anti-tissue transglutaminase antibodies in patients with irritable bowel syndrome in Duhok city / Prevalência de anticorpos antitransglutaminase tecidual em pacientes com síndrome do intestino irritável na cidade de Duhok

Abstract Background Irritable bowel syndrome (IBS) is a common gastrointestinal disorder; celiac disease is an autoimmune enteropathy that can mimic any functional gastrointestinal disorder. The aim of this study is to estimate the prevalence of celiac disease antibodies (anti Tissue Transglutaminase-tTG) in patients with irritable bowel syndrome. Patients and methods This cross sectional study was conducted on 70 patients with irritable bowel syndrome fulfilling Rome III criteria who visited Azadi Teaching Hospital in Duhok city-Iraq. Patients were classified according to irritable bowel syndrome subtypes into: Diarrhoea Predominant (D-IBS), Constipation Predominant (C-IBS) and Mixed (M-IBS). IgA and IgG anti tTG were used to screen patients for celiac disease. Results A total number of 70 patients (44 females and 26 males) were included; their mean age was 33 years (SD ± 7.64). Five patients (7.1%) were found to have positive both IgA and IgG anti tTG. Three of them have had D-IBS and the other two had C-IBS. No one of the M-IBS patients tested positive. Conclusion The prevalence of anti tTG antibodies in irritable bowel syndrome is high. Patients with D-IBS should be screened for celiac disease.

Resumo Introdução A síndrome do intestino irritável (SII) é um distúrbio gastrointestinal comum; a doença celíaca é uma enteropatia autoimune que pode imitar qualquer distúrbio gastrointestinal funcional. O objetivo deste estudo foi estimar a prevalência de anticorpos contra a doença celíaca (antitransglutaminase tecidual - tTG) em pacientes com SII. Pacientes e Métodos Este estudo transversal foi conduzido em 70 pacientes com síndrome do intestino irritável que atendiam aos critérios de Roma III e se apresentaram ao Hospital de Ensino Azadi na cidade de Duhok, no Iraque. Os pacientes foram classificados de acordo com os subtipos de síndrome do intestino irritável em: predominantemente diarreia (D-SII), predominantemente constipação (C-SII) e mista (M-SII). IgA e IgG antitTG foram usados para rastrear pacientes com doença celíaca. Resultados Um total de 70 pacientes (44 mulheres e 26 homens) foram incluídos; a idade média foi de 33 anos (DP ± 7,64). Cinco pacientes (7,1%) apresentaram IgA e IgG antitTG positivos. Três deles tinham D-SII e os outros dois tinham C-SII. Nenhum dos pacientes com M-SII apresentou teste positivo. Conclusão A prevalência de anticorpos antitTG na SII é alta. A presença de doença celíaca deve ser avaliada em pacientes com D-SII.

Niveles de IgA en adultos con enfermedad celíaca / IgA levels in adults with celiac disease

La enfermedad celíaca (EC) es una enfermedad autoinmune sistémica desencadenada por el consumo de gluten de la dieta en personas con susceptibilidad genética. Los principales test serológicos utilizados para el diagnóstico y seguimiento de la EC son pruebas basadas en anticuerpos de isotipo inmunoglobulina (Ig) A, siendo la determinación de IgA anti-transglutaminasa tisular (tTG)2 la prueba serológica inicial de elección. La deficiencia selectiva de IgA (DSIgA), es más prevalente en pacientes con EC que en la población general, dificultando el diagnostico serológico de la enfermedad. En el presente estudio observacional descriptivo, se incluyeron 74 pacientes adultos con diagnóstico confirmado de EC y se determinó IgA anti-tTG2 en suero mediante ensayo de ELISA a fin de detectar a aquellos pacientes con niveles indeterminados o negativos, los cuales podrían presentar DSIgA. Se dosó IgA total en el suero de estos pacientes por inmunodifusión radial y el promedio fue de 237,8 ± 100,6 mg/dL. En una paciente del sexo femenino fue detectada IgA total menor a 7 mg/dL, con niveles séricos de IgG e IgM normales, característicos de la DSIgA. Así, la frecuencia calculada de DSIgA fue de 1,35% en la población con EC estudiada. En conclusión, este trabajo es una primera aproximación para describir la frecuencia de DSIgA en pacientes con EC del país y reafirma la importancia de incluir el dosaje de IgA total en el caso de realizar test serológicos de la EC basados en IgA(AU)

Anticuerpo anti-transglutaminasa tisular en adultos con enfermedad celíaca y su relación con la presencia y duración de la dieta libre de gluten / Anti-transglutaminase antibody in adults with celiac disease and their relation to the presence and duration of gluten-free diet

Introducción: El anticuerpo IgA anti-transglutaminasa tisular 2 (tTG2) es un marcador relevante de la enfermedad celíaca. La utilidad de la determinación de IgA anti-tTG2 está bien establecida para el diagnóstico de la patología, sin embargo su uso para el seguimiento de pacientes con dieta libre de gluten (DLG) no se encuentra del todo esclarecido. Objetivo: Determinar los niveles de IgA anti-tTG2 en pacientes adultos paraguayos con enfermedad celíaca y su relación con la presencia y duración de la DLG. Materiales y métodos: En este estudio observacional descriptivo con componente analítico, transversal, se incluyeron pacientes celíacos adultos, sin (n=23) o con (n=49) DLG. Se determinaron por ELISA los niveles séricos de IgA anti-tTG2. Resultados: Todos (100%) los pacientes celíacos sin DLG presentaron niveles séricos positivos de IgA anti-tTG2. Se observaron niveles séricos de IgA anti-tTG2 significativamente elevados en pacientes celíacos sin DLG en comparación con los niveles en pacientes con DLG. El 35% de los pacientes en tratamiento con DLG (promedio de duración de la dieta = 5,7 años) presentaron niveles positivos (29%) o indeterminados (6%) de IgA anti-tTG2. En relación con la duración de la DLG se observó que al aumentar el tiempo de DLG disminuyen los niveles del auto-anticuerpo (r=-0,2963; p=0,0387). Conclusiones: Los niveles de IgA anti-tTG2 se correlacionaron inversamente con la duración de la DLG. Sin embargo, niveles positivos del anticuerpo persistieron en algunos pacientes, incluso varios años después del inicio de la DLG.

IgA anti-transglutaminase 2 (tTG2) antibody is a relevant marker in celiac disease. The utility of IgA anti-tTG2 determination is well established for the diagnosis, however their use in the follow-up of patients with gluten free diet (GFD) it is not fully established. Objective: To determine IgA anti-tTG2 antibody levels in adult Paraguayan celiac disease patients and its relation to the presence and duration of the GFD. Materials and methods: Adult celiac disease patients without (n=23) or with (n=49) GFD were included in this observational, descriptive, cross-sectional study with analytical component. IgA anti-tTG2 antibody serum levels were analyzed by ELISA. Results: All (100%) celiac disease patients without GFD had positive anti-tTG2 IgA. Serum levels of IgA anti-tTG2 were significantly elevated in celiac disease patients without GFD compared to levels in patients with GFD. 35% of patients treated with GFD (diet average duration = 5.7 years) had positive (29%) or indeterminate (6%) levels of IgA anti-tTG2. In terms of GFD duration we observed that while the GFD period increased, antibody levels decreased (r=0.2963; p=0.0387). Conclusion: IgA anti-tTG2 antibody levels correlated inversely with the GFD duration. However, positive levels of these antibodies persisted in some patients, even several years after the onset of GFD.

Estado inmunonutricional de adultos celíacoss atendidos en el Instituto de Gastroenterología, 2016-2017 / Immune-nutritional status of celiac adults treated at the Institute of Gastroenterology, 2016-2017

Introducción: La enfermedad celíaca es uno de los trastornos crónicos más comunes que afecta a los habitantes de todo el mundo. Con la ruptura del equilibrio inmunonutricional se compromete la evolución clínica de estos pacientes. Objetivo: Caracterizar el estado inmunonutricional de adultos celíacos atendidos en el Instituto de Gastroenterología. Material y Métodos: Se realizó un estudio observacional descriptivo transversal en 43 adultos celíacos atendidos en el Instituto de Gastroenterología de La Habana, en el período comprendido entre marzo de 2016 y marzo 2017. A todos, previo consentimiento informado, se les realizó mensuraciones antropométricas, encuesta dietética, hemograma completo, dosificación de inmunoglobulinas totales y estudios bioquímicos. Resultados: El 53,5 por ciento de los pacientes tuvo algún trastorno de malnutrición por exceso o por defecto. El 44 por ciento presentó anemia y 14 por ciento hipercolesterolemia. En 9,3% se observó hipogammaglobulinemia para IgM, en 4,7 por ciento, paraIgG y también en 4,7 por ciento, para IgA. El antecedente patológico personal más frecuente fue el de giardiasis con 16,3 por ciento. Ningún paciente refirió la ingesta de mariscos ni cereales con gluten, 9 fueron positivos a antitransglutaminasa tisular, lo que indica mal control dietético, de ellos 88,8 por ciento de los casos se detectaron en los grupos con índice de masa corporal por debajo del peso adecuado. Conclusiones: El estado inmunonutricional inadecuado es frecuente en los adultos celíacos atendidos en el Instituto de Gastroenterología. La no adherencia a la dieta libre de gluten y la elevada frecuencia de malnutrición(AU)

Introduction: Celiac disease is one of the most common chronic disorders that affects people all over the world. The clinical evolution of these patients is compromised with the breakdown of the immune-nutritional balance. Objective: To characterize the immune-nutritional status of celiac adults treated at the Institute of Gastroenterology. Material and Methods: A cross-sectional descriptive observational study was conducted in 43 celiac adults treated at the Institute of Gastroenterology of Havana, in the period between March 2016-March 2017. With prior informed consent, all of them were given anthropometric measurements, dietetic survey, complete blood count, total doses of immunoglobulin, and biochemical studies. Results: The 53,5 percent of patients had some malnutrition disorders due to excess or defect. The 44 percent presented anemia, and the 14 percent presented hypercholesterolemia. IgM Hypogammaglobulinemia was observed in 9,3 percent; IgG and IgA Hypogammaglobulinemia were also observed in a 4,7 percent as well as 4,7 percent respectively. The most frequent personal pathological antecedent was that of giardiasis with 16,3 percent. No patient reported the intake of shellfish or cereals containing gluten, 9 were positive to tissue anti-transglutaminase, indicating poor dietary control, of which 88,8 percent of cases were detected in groups with a body mass index below the appropriate weight. Conclusions: Inadequate immuno-nutritional status is frequent in celiac adults treated in the Institute of Gastroenterology. Non-adherence to a gluten-fre(AU)

Potencial associação da doença celíaca com anemia ferropriva refratária em crianças e adolescentes / Association of potential celiac disease and refractory iron deficiency anemia in children and adolescents

ABSTRACT BACKGROUND: Celiac disease is an enteropathy caused by dietary gluten. The combination of serologic, genetic and histologic data has led to description of other categories of this disease. OBJECTIVE: There are a number of patients with iron deficiency anemia (IDA) that do not respond to iron treatment and may be repeated for many times, Therefore, we aimed to investigate celiac disease in this group. METHODS: In this cross sectional transverse prospective study from August 2011 to February 2013, in a Pediatric care clinic affiliated to Shiraz University of Medical Sciences, 184 children including 92 IDA patients who responded to treatment using iron supplement, 45 non-responding iron deficient patients, and 47 healthy individuals, with the maximum age of 18 years, with written consent from their parents, participated in serologic screening (with Anti-TTG antibody and anti-Endomysial antibody) for celiac disease. Patients with at least one positive serology test underwent multiple mucosal biopsy from bulb and duodenum. RESULTS: Among 184 participants, 19 (10.3%) subjects had positive serologic test for celiac disease, including 13 (28.9%) patients in the group with refractory IDA, 5 (5.4%) patients in the group with treated IDA, and 1 patient in the healthy group. The frequency of positive serologic test in the group with IDA resistant to treatment was prominently higher than the other two groups (P<0.001). Among the patients with positive serologic celiac test who underwent endoscopy and biopsy, no histologic evidence of celiac disease was seen. They were diagnosed as potential celiac disease. CONCLUSION: Frequency of potential celiac disease in patients with refractory IDA was higher than control the subjects. Therefore, we recommend serologic screening for early detection and minimizing the complications of celiac disease and repeated iron therapy for this group.

RESUMO CONTEXTO: A doença celíaca é uma enteropatia causada pelo glúten na dieta. A combinação de dados sorológicos, genéticos e histológicos proporcionou a descrição de outras categorias desta doença. OBJETIVO: Há pacientes com anemia por deficiência de ferro que não respondem ao tratamento com ferro mesmo que repetido por muitas vezes. O objetivo deste trabalho foi investigar a presença de doença celíaca nestes indivíduos. MÉTODOS: Realizado estudo prospectivo com cruzamento secional transversal, de agosto de 2011 a fevereiro de 2013, em uma clínica de cuidados pediátricos afiliados a Shiraz University Medical Sciences, com 184 crianças incluindo 92 pacientes com anemia por deficiência de ferro que responderam ao tratamento com ferro suplementar, 45 não respondedores e 47 indivíduos sadios, com idade máxima de 18 anos, todos com consentimento informado dos pais. Todos participaram da triagem sorológica (com anticorpos anti-TTG e anticorpo antiendomísio) para doença celíaca. Pacientes com pelo menos um teste de sorologia positiva foram submetidos a biópsia da mucosa múltipla do bulbo e duodeno. RESULTADOS: Entre os 184 participantes, 19 (10,3%) tinham teste sorológico positivo para doença celíaca, incluindo 13 (28,9%) pacientes no grupo com a anemia por deficiência de ferro refratária, 5 (5,4%) pacientes no grupo com anemia por deficiência de ferro tratados e respondedores e 1 paciente do grupo saudável. A frequência de teste sorológico positivo no grupo com anemia por deficiência de ferro resistente ao tratamento foi destacadamente maior do que os outros dois grupos (P<0,001). Entre os pacientes com teste sorológico positivo para doença celíaca submetidos a endoscopia e biópsia, não foi vista nenhuma evidência histológica de doença celíaca. Foram diagnosticados como potencial doença celíaca. CONCLUSÃO: Potencial frequência de doença celíaca em pacientes com anemia por deficiência de ferro refratária foi maior do que nos controles. Portanto, recomendamos testes sorológicos de triagem para a detecção precoce, minimizando as complicações da terapia de ferro repetidas para este grupo.

Tratamiento de la enfermedad celíaca: ¿Cómo medir adherencia a la dieta libre de gluten? / Treating coeliac disease: How do we measure adherence to the gluten-free diet?

La enfermedad celíaca (EC) es un trastorno sistémico inmune mediado por la ingesta de gluten en individuos genéticamente susceptibles. Se caracteriza por manifestaciones clínicas variables, auto anticuerpos anti-endomisio, anti-transglutaminasa (tTG) y/o anti-péptidos de gliadina deamidados (PGD) en sangre, más daño variable de la mucosa intestinal. En Chile el 0,76% de los mayores de 15 años tiene IgA-tTG positiva y la prevalencia de EC se estima en ~0,6%. En familiares de primer grado de celíacos se ha identificado ~17% de casos tTG positivos. Hasta hoy el único tratamiento es la dieta libre de gluten (DLG), que para ser efectiva debe ser estricta, permanente y durante toda la vida. La DLG no contiene cero gluten, sino que lo disminuye hasta un «punto de corte¼, que en Chile es 3 ppm (o mg/kg de producto). La mortalidad de la EC es mayor que la de la población general, y la falta de adherencia al tratamiento se asocia a complicaciones (procesos autoinmunes y cáncer principalmente). La DLG es difícil de mantener estrictamente, y las transgresiones son por lejos la principal causa de falta de respuesta al tratamiento. El seguimiento también es difícil, porque no existen marcadores objetivables que midan la adherencia. En la práctica clínica se utiliza la medición de auto anticuerpos anti-endomisio, tTG y/o PGD; más recientemente se están evaluando las entrevistas por una nutricionista especializada, cuestionarios validados y la medición de péptidos 33-mer en heces como alternativas o complementos de la evaluación de adherencia. En este artículo se revisan las herramientas de seguimiento actualmente utilizadas, poniendo énfasis en aquellas disponibles en Chile.

Coeliac disease (CD) is a systemic autoimmune disorder triggered by gluten consumption in genetically susceptible individuals. It exhibits several clinical features, such as blood auto-antibodies (anti-endomysial antibodies EMA, anti-transglutaminase antibodies tTG, anti-deamidated gliadin peptides PGD), plus variable degrees of damage in the small intestinal mucosa. In Chile, tTG is positive in 0.76% in individuals >15 years, with the prevalence of CD being estimated at 0.6%. Approximately17% of first-degree relatives of coeliac patients have been reported tTG positive. To date, the gluten free diet (GFD) is the only known treatment for CD. To be effective, this must be lifelong, permanent, and strict. Gluten content in the GFD is not zero, but is limited to a cut-off of 3 ppm (or mg/kg of product) in Chile. Mortality higher than that of the general population has been reported among coeliac patients, and poor adherence to GFD is associated with complications (mainly autoimmune processes and cancer). GFD is difficult to maintain strictly and poor adherence is by far the main cause of lack of response to treatment. Follow-up of adherence is also difficult because there are no objective measurements to assess it. In clinical practice determination of serum EMA, tTG and PGD is routinely used for these purposes, although more recently, the interview by an expert dietitian, validated questionnaires and measurement of faecal 33-mer peptide are being assessed as alternatives or complements to measure adherence to GFD. A review is presented with the current concepts on the available tools to follow up patients on GFD, emphasising those available in Chilel.

Frecuencia de anticuerpos anti-transglutaminasa y antiendomisio en pacientes con diabetes tipo 1 / Association of type 1 diabetes mellitus with celiac disease

Background: Type 1 diabetes mellitus and celiac disease share common genetic and immunological aspects and celiac disease is more common among type 1 diabetic patients. Aim: To determine the frequency of anti endomysial and anti transglutaminase antibodies among patients with type 1 diabetes. Material and Methods: Anti endomysialantibodies determined by indirect immunofluorescence an anti transglutaminase antibodies determined by ELISA were measured in 410 serum samples of patients with type 1 diabetes. Results: Seventy one samples (17 percent) had positive anti transglutaminase antibodies. Among these, 17 had also positive anti endomysial antibodies. In 11 of these 17 patients, the presence of celiac disease was confirmed. Conclusions: Among patients with type 1 diabetes mellitus, the frequency of celiac disease is three times higher than in the general population.

Péptidos inmunogénicos del gluten en deposiciones: nuevo método para evaluar la adherencia a la dieta en pacientes celíacos / Immunogenic gluten peptides in stools: new method to evaluate in the dietary adherence in celiac patients

Celiac disease (CD) is an autoimmune pathology caused by the ingestion of gluten in genetically susceptible people, currently considered multisystemic. The treatment of CD is a lifelong strict Gluten-Free Diet (GFD), which allows a symptomatic improvement in most patients and achieve intestinal mucosa healing confirmed with histological study. The adherence to the GFD is variable, arguing as possible factors related to failure the economic, cultural, social aspects and the consumption of gluten inadvertently. The management of celiac patients contemplates instructing in the proper follow-up of GFD and evaluating their adherence. So far, the only way to assess adherence to GFD is through surveys, self-reports of eating habits and serology, being the main disadvantage the subjectivity factor. Recently the immunogenic gluten peptides have acquired relevance for the objective evaluation of the adherence to the GFD and the measurement appears as an efficient and sensitive option to determine the gluten intake, providing relevant information for the clinical management.

Enfermedades autoinmunitarias asociadas a diabetes mellitus tipo 1A / Autoimmune diseases in type 1A diabetes mellitus

Type 1A diabetes (DM1A) is an autoimmune disease that comprises 10% of patients with diabetes mellitus. Its frequency is gradually increasing in countries like Mexico. Patients with DM1A commonly have hypothyroidism, Addison disease, celiac disease and less common diseases such as polyglandular syndrome. These diseases are related to susceptibility genes such as HLA, CTLA-4 and PTPN22, which induce central and peripheral immunologic tolerance. This review article emphasizes the importance of searching other autoimmune diseases in patients with DM1A, to improve their prognosis and quality of life.

Aspectos inmunológicos de la enfermedad celíaca / Immunological aspects of celiac disease

La enfermedad celíaca (EC) es un trastorno inflamatorio crónico del intestino delgado inducido por la ingestión de gluten de trigo y otras prolaminas de cereales como cebada, centeno o avena. Afecta a las personas con susceptibilidad genética, y se manifiesta por una lesión de la mucosa intestinal (con linfocitosis intraepitelial, pérdida de vellosidades y remodelación tisular), y la presencia de anticuerpos antitransglutaminasa. El modelo patogénico más aceptado se basa en la activación de una respuesta de la inmunidad adaptativa tras la estimulación de linfocitos T CD4+ mediante péptidos de gluten modificados por la enzima transglutaminasa tisular presentados junto a moléculas HLA-DQ2 o DQ8, y la producción de citoquinas y otros mediadores pro inflamatorios. El gluten activa también la inmunidad innata local y los mecanismos de citotoxicidad sobre el epitelio mediados por linfocitos intraepiteliales. Aunque no se conoce bien cuál es el efecto o la implicación patogénica de los anticuerpos específicos de la EC, la disponibilidad de marcadores serológicos e inmunogenéticos como herramientas diagnósticas ha propiciado el avance en el conocimiento de la EC, y la revisión de los criterios diagnósticos, especialmente en los individuos adultos con expresión mínima o atípica de la enfermedad...

Positividad anticuerpo antitransglutaminasa tisular humana en adultos histológicamente compatibles con enfermedad celíaca / Antitransglutaminase antibody positivity in adults histologically compatible with celiac disease

Objetivo: Determinar la frecuencia de positividad de anticuerpo antitransglutaminasa tisular humana en pacientes adultos histológicamente compatibles con enfermedad celiaca. Material y método: El presente trabajo corresponde a un diseño analítico, transversal con régimen de investigación orientado, en el que se realizó una revisión de historias clínicas de pacientes del Servicio de Gastroenterología de la Clínica San Pablo, Lima, Perú, con resultados de biopsias compatible con enfermedad celíaca (EC) desde el año 1994 al 2011 y que además contó con valor de anticuerpo antitransglutaminasa tisular humana (AATG), calculándose la frecuencia de positividad del mismo. Resultados: Según criterios señalados por el presente estudio se trabajó sobre un total de 44 historias clínicas conformadas por 18 (40,9%) correspondientes a hombres y 26 (59,1%) a mujeres, con una edad media al momento del diagnóstico de 51 ± 16,23 años en general de las cuales 12 (27,27%) obtuvieron resultado positivo para AATG, 2 (4,54%) valores indeterminados y 30 (68,18%) resultados negativos con resultados histológico compatible con EC. Conclusión: No es frecuente la positividad del anticuerpo antitransglutaminasa tisular humana en pacientes adultos histológicamente compatibles con enfermedad celiaca.

Objective: To determine the frequency of positive results for antitransglutaminase antibody in adult patients histologically compatible with celiac disease. Material and methods: Cross sectional, descriptive study with research-oriented regime, which included medical records of Gastroenterology Service of San Pablo Clinic, Lima, Peru from 1994 to 2011 with biopsies histologically compatible with CD and antitransglutaminase antibodies to find the frequency of positive serology. Results: According to criteria established by the present study, we worked on a total of 44 medical records which included18 (40.9%) men and 26 (59.1%) women, mean age at diagnosis of 51 ± 16.23 years at the total. From all, 12 (27.27%) were positive for AATG, 2 (4.54%) values were indeterminate and 30 (68.18%) were negative with histological findings compatible with CD. Conclusion: It is not frequent positive results for antitransglutaminase antibody in adult patients histologically compatible with celiac disease.

Rastreio de síndrome poliglandular autoimune em uma população de pacientes com diabetes melito tipo 1 / Screening for autoimmune polyglandular syndrome in a cohort of patients with type 1 diabetes mellitus

OBJETIVO: Caracterizar uma população de pacientes com diabetes melito tipo 1 (DMT1) relativamente à presença de outras entidades autoimunes que permitam estabelecer o diagnóstico de síndrome poliglandular autoimune (SPGA). SUJEITOS E MÉTODOS: Incluímos 151 pacientes com DMT1. Analisamos os seguintes parâmetros clínicos: gênero, idade atual, duração da doença, antecedentes pessoais de patologia autoimune e antecedentes familiares de diabetes melito. Submetemos cada doente a um estudo laboratorial com o objetivo de detectar a presença de marcadores imunológicos para a tireoidite, insuficiência adrenocortical, gastrite e doença celíaca, e eventual disfunção associada. RESULTADOS: Coorte com 51,7% homens, idade média atual de 33,4 ± 13 anos e duração da doença de 14,4 ± 9,6 anos. Antecedentes pessoais de autoimunidade presentes em 2% da amostra e história familiar de diabetes melito em 31,1%. A frequência de marcadores imunológicos foi de 24% para a tireoidite, 9,4% para a insuficiência adrenocortical, 17,2% para a gastrite e 2% para a doença celíaca. Foi diagnosticada SPGA em 25,2% dos pacientes. O risco de SPGA e tireoidite autoimune foi superior em mulheres. A duração da doença correlacionou-se diretamente com a presença de autoanticorpos gástricos e inversamente com a positividade dos anticorpos anti-ilhota, antiglutamato descarboxilase e antitirosina fosfatase. Constatou-se a existência de uma associação entre os marcadores imunológicos da tireoidite e gastrite, bem como entre a doença celíaca e insuficiência adrenocortical. CONCLUSÃO: Atendendo à frequência e ao prognóstico inerente à SPGA, a necessidade de realizar rastreio em pacientes com DMT1 é enfatizada. O diagnóstico atempado de outras doenças autoimunes permitirá individualizar o tratamento e seguimento do doente.

OBJECTIVE: To characterize a cohort of patients with type 1 diabetes mellitus (T1DM) on the presence of other autoimmune disorders that could establish the diagnosis of autoimmune polyglandular syndrome (APS). SUBJECTS AND METHODS: We included 151 patients with T1DM. The following clinical parameters were analyzed: gender, current age, disease duration, previous history of autoimmune disorders, and familial history for diabetes mellitus. Each patient was analyzed to detect autoimmune markers of thyroiditis, adrenocortical insufficiency, gastritis, and celiac disease, as well as possible associated dysfunctions. RESULTS: A cohort with 51.7% males, average current age of 33.4 ± 13 years and disease duration of 14.4 ± 9.6 years was analyzed. Previous history of autoimmunity was found in 2%, and familial history for diabetes mellitus in 31.1% of the cohort. Frequency of autoimmune markers was 24% for thyroiditis, 9.4% for adrenocortical insufficiency, 17.2% for gastritis, and 2% for celiac disease. APS was diagnosed on 25.2% of the patients. APS and autoimmune thyroiditis risk was higher in females. Disease duration correlated directly with gastric autoantibodies, and inversely with positive islet cell, glutamic acid decarboxylase, and tyrosine phosphatase antibodies. We noticed a correlation between autoimmune markers for thyroiditis and gastritis, as well as between celiac disease and adrenocortical insufficiency. CONCLUSION: Considering APS prevalence and prognosis, the need for APS screening in patients with T1DM is emphasized. Early diagnosis of other autoimmune disorders will enable us to adjust each patient treatment and follow-up.

Review: dermatitis herpetiformis / Revisao: dermatite herpetiforme

Dermatitis herpetiformis (DH) or Duhring-Brocq disease is a chronic bullous disease characterized by intense itching and burning sensation in the erythematous papules and urticarial plaques, grouped vesicles with centrifuge growth, and tense blisters. There is an association with the genotypes HLA DR3, HLA DQw2, found in 80-90% of cases. It is an IgA-mediated cutaneous disease, with immunoglobulin A deposits appearing in a granular pattern at the top of the dermal papilla in the sublamina densa area of the basement membrane, which is present both in affected skin and healthy skin. The same protein IgA1 with J chain is found in the small intestinal mucosa in patients with adult celiac disease, suggesting a strong association with DH. Specific antibodies such as antiendomysium, antireticulina, antigliadin and, recently identified, the epidermal and tissue transglutaminase subtypes, as well as increased zonulin production, are common to both conditions, along with gluten-sensitive enteropathy and DH. Autoimmune diseases present higher levels of prevalence, such as thyroid (5-11%), pernicious anemia (1-3%), type 1 diabetes (1-2%) and collagen tissue disease. The chosen treatment is dapsone and a gluten-free diet.

Dermatite herpetiforme é uma doença bolhosa crônica caracterizada por intenso prurido e sensação de queimação em pápulas eritematosas e placas urticariformes, vesículas agrupadas com crescimento centrífugo e bolhas tensas. Apresenta associação com genótipos de HLA DR3, HLA DQW2 encontrados em 80 a 90% dos casos. É uma doença cutânea mediada por IgA com depósito de imunoglobulina A em padrão granular no topo da papila dérmica na área da sublâmina densa na zona da membrana basal, presente tanto na pele lesada com em área de pele sã. A mesma cadeia J da proteína IgA1 é encontrada na mucosa do intestino delgado em pacientes com doença celíaca do adulto, sugerindo forte associação com a dermatite herpetiforme. Anticorpos específicos com anti-endomísio, anti-reculina, anti-gliadina, e recentemente identificado, o subtipo transglutaminase epidérmica e tecidual, assim como a produção aumentada da zonulina, são descritas em ambas as afecções enteropatia sensível ao glúten e a deramtite herpetiforme. Exibe depósitos de IgA em padrão granular na papila dérmica. Doenças auto-imunes exibem maior prevalência como tireoidopatia em 5 a 11%, anemia perniciosa em 1 a 3%, diabetes tipo 1 em 1 a 2% e doença do colágeno. O tratamento de escolha é a dapsona e dieta isenta de glútem.

Estudo da prevalência da doença celíaca em crianças e adolescentes com diabetes melito tipo 1: resultado de 10 anos de acompanhamento / Study of prevalence of celiac disease in children with type 1 diabetes mellitus: result of 10 years of follow-up

OBJETIVO: Avaliar a prevalência da doença celíaca (DC) em crianças e adolescentes com diabetes melito tipo 1 (DM1) atendidos no Serviço de Endocrinologia Pediátrica do Hospital das Clínicas da Universidade Federal de Minas Gerais. SUJEITOS E MÉTODOS: Incluídos no estudo crianças e adolescentes com diagnóstico prévio de DM1 acompanhadas no serviço no período de março de 1999 a abril de 2009, com idades entre zero e 18 anos. Todos foram rastreados para DC na primeira consulta e anualmente. A investigação foi realizada por meio da dosagem dos anticorpos da classe IgA (AGAA) e IgG (AGAG) antigliadina. Os pacientes com AGAA e/ou AGAG acima de duas vezes o valor de referência foram submetidos à biópsia intestinal. RESULTADOS: Foram excluídos 21 pacientes do total inicial de 384. Destes, 50 tiveram a sorologia positiva e 29 foram submetidos à biópsia intestinal. A prevalência encontrada foi de 3,1%. CONCLUSÃO: O rastreamento periódico da DC nos pacientes diabéticos deve ser encorajado, dada sua alta prevalência.

OBJECTIVE: To estimate the prevalence of celiac disease (CD) in children and adolescents with type 1 diabetes mellitus (T1DM) treated in the Children's Division of Endocrinology, at the Universidade Federal de Minas Gerais Hospital das Clínicas. SUBJECTS AND METHODS: Children and adolescents diagnosed with T1DM, aged 0 to 18 year, were included in this study performed from March 1999 to April 2009. All patients were screened for CD at their first visit and, again, annually. The investigation was performed through the measurement of IgA (AGAA) and IgG (AGAG) antigliadin antibodies. Patients with values of AGAA and/or AGAG above two times the cutoff mark undertook intestinal biopsy. RESULTS: A group of 21 patients were excluded from the initial total of 384 patients. Out of the remaining, 50 patients had positive serology and 29 underwent intestinal biopsy. The prevalence index was 3.1%. CONCLUSION: The periodic screening of CD in diabetic patients should be encouraged, due to its high prevalence.

Vitiligo and autoantibodies of celiac disease

Vitiligo is an acquired, idiopathic disorder characterized by circumscribed depigmented macules and patches. The exact etiology and pathogenesis of vitiligo is not clear. Many theories have been presented regarding this subject among them aautoimmune theory is the most important one. The association of vitiligo with other autoimmune disorders has been reported, but the relationship between vitiligo and celiac disease is controversial. The aim of this study was to study the frequency of celiac autoantibodies in a group of vitiligo patients compared with control. This was a cross sectional case control study that involved 128 individuals, 64 vitiligo patients and 64 individuals as control group. The means age of participants was 30.3 +/- 14.4 years. IgA anti Endomysial antibody and IgA anti-glutaminase antibody were measured by ELISA method in the serum of all participants. Data were analyzed by SPSS software version 15. The serum of two vitiligo patients [3.1%] was positive for antibodies. All control groups were seronegative for these antibodies [P < 0.05]. There was nosignificant effect of sex and job on seropositivity. There may be a relationship between celiac disease and vitiligo. This may indicate a common basic autoimmune mechanism that is an explanation for few case reports that gluten free diets were effective in the treatment of vitiligo patients. Both T test and exact fisher test showed no effect of age, sex and job anseropositivity of these patients [p=0.56 and p=0.74, respectively]

Prevalência de doença celíaca em crianças e adolescentes com miocardite e cardiomiopatia dilatada / Celiac disease prevalence in children and adolescents with myocarditis and dilated cardiomiopathy

OBJETIVO: Determinar a prevalência de doença celíaca em pacientes portadores de cardiomiopatia dilatada e miocardite. MÉTODOS: Foram avaliados 56 pacientes, com idade entre 1 e 18 anos, portadores de cardiomiopatia dilatada ou miocardite, acompanhados no Instituto Materno Infantil Professor Fernando Figueira. Foram excluídos pacientes com diagnóstico prévio de doença celíaca. A classe funcional da insuficiência cardíaca foi determinada segundo os critérios da American Heart Association, como classe funcional I, II, III e IV. O diagnóstico de miocardite foi relatado em prontuário, e o de cardiomiopatia dilatada, pelo ecocardiograma, a partir da presença de disfunção sistólica de um ou ambos os ventrículos, com fração de ejeção menor que 55% e dilatação ventricular, com diâmetro diastólico final ventricular esquerdo maior que 112%. Nos pacientes incluídos no estudo, foi aplicado um formulário com informações sobre sintomatologia gastrointestinal e cardiológica; em seguida, dosadas sorologias para anticorpos antitransglutaminase tecidual humana e antiendomísio. Aqueles com sorologia positiva foram encaminhados à biópsia intestinal para avaliação histológica para doença celíaca, segundo os critérios de Marsh. RESULTADOS: Uma das 56 crianças apresentou sorologia antitransglutaminase positiva (1,8%), porém anticorpo antiendomísio negativo. A histologia intestinal demonstrou atrofia total das vilosidades. Cerca de 30% dos pacientes apresentaram insuficiência cardíaca. Sinais e sintomas gastrointestinais foram frequentes nos pacientes, em especial dor abdominal (70%, 39/56). CONCLUSÃO: A frequência de doença celíaca em pacientes com cardiomiopatia dilatada e miocardite foi de 1,8%. É importante investigar doença celíaca nos pacientes com essas doenças cardíacas para evitar evolução das doenças e deterioração clínica do paciente.

OBJECTIVE: To determine the prevalence of celiac disease in patients with myocarditis and dilated cardiomyopathy. METHODS: Fifty-six patients between 1 and 18 years old with dilated cardiomyopathy or myocarditis were evaluated and followed up at Instituto de Medicina Integral Professor Fernando Figueira. Patients with previous diagnosis of celiac disease were excluded. The functional classification was determined according to the American Heart Association criteria (classes I, II, III and IV). Diagnosis of myocarditis was reported in the patients' medical records. Dilated cardiomyopathy was diagnosed by echocardiogram with systolic dysfunction of one or both ventricles, ejection fraction lower than 55%, ventricular dilatation, and left ventricular diastolic diameter bigger than 112%. Patients answered a questionnaire about gastrointestinal and cardiac symptoms; next, anti-tissue transglutaminase (tTG) and anti-endomysial (EMA) antibodies were dosed. Those with positive antibody results were referred to intestinal biopsy and histological evaluation to detect celiac disease according to Marsh classification. RESULTS: One of the 56 children (1.8%) had positive tTG antibody level, but negative EMA. Intestinal histological evaluation showed total villous atrophy. Approximately, 30% of patients had heart failure. Gastrointestinal symptoms and signs were frequent, especially abdominal pain (70%, 39/56). CONCLUSION: Celiac disease prevalence in pediatric patients with dilated cardiomyopathy or myocarditis was 1.8%. It is important to investigate celiac disease in patients with these conditions to avoid the progression of such diseases and patients' clinical deterioration.

Autoantibodies in relatives of celiac disease patients: a follow-up of 6-10 years / Autoanticorpos em familiares de pacientes celíacos: seguimento por 6 a 10 anos

CONTEXT: Autoimmune diseases are 3 to 10 times more frequently in patients with celiac disease and their relatives than in the general population. OBJECTIVE: To investigate a broad spectrum of autoantibodies in celiac disease relatives from Southern Brazil, in a serological follow-up of 6-10 years, aiming to associate with other autoimmune diseases, degree of parentage, demographic and clinical data. METHODS: Serum samples of 233 relatives were analyzed in two different phases: n = 186 in phase I (1997-2000) and n = 138 (being 91 = follow-up group and 47 = newly tested) in phase II (2006-2007). As controls, 100 unrelated individuals were evaluated. Autoantibodies to smooth muscle, mitochondrial, liver-kidney microssome, parietal cell and thyroid microssome were tested by indirect immunofluorescence. RESULTS: A significant increase of autoantibodies, in both phases, was observed in the relatives when compared to the non-relatives (P = 0.0064), specifically to anti-thyroid microssome and anti-parietal cell. In both phases, the female/male proportion of autoantibodies was of 4:1 to 3:1 (P<0.041). The frequency of autoantibodies amongst 1st and 2nd degree relatives was 11.8% and 9.68% in phase I and 4% and 6.67% in phase II. CONCLUSION: Celiac disease relatives presented other autoantibodies and serological screening is a useful instrument for identifying autoimmune diseases along the years.

CONTEXTO: Doenças autoimunes são 3 a 10 vezes mais frequentes em pacientes com doença celíaca e em seus familiares que na população em geral. OBJETIVOS: Realizar amplo perfil de autoanticorpos em familiares de celíacos do sul do Brasil, em seguimento sorológico de 6-10 anos, visando associá-lo com outras doenças autoimunes, grau de parentesco, dados demográficos e clínicos desses indivíduos. MÉTODOS: Foram analisadas amostras de 233 familiares em duas etapas diferentes: n = 186 na etapa I (1997-2000) e n = 138 (91 recoleta e 47 novos familiares testados) na etapa II (2006-2007). Como controle foram avaliadas amostras de 100 não-familiares. Anticorpos antimúsculo liso, antimitocondrial, anticélula gástrica parietal, antimicrossomal de fígado e rim e antimicrossomal tireoidiano foram testados por imunofluorescência indireta. RESULTADOS: Foi observado um aumento significativo de positividade para os autoanticorpos em familiares de celíacos, quando comparados aos não-familiares (P = 0,0064), especificamente para o antimicrossomal tireoidiano e anticélula gástrica parietal. Entre os indivíduos com autoanticorpos positivos, a proporção do sexo feminino para o masculino foi de 4:1 e 3:1 em ambas as etapas (P<0,041). A frequência de autoanticorpos detectada entre familiares de primeiro e segundo graus foi de 11,8% e 9,68% na etapa I e 4% e 6,67% na etapa II. CONCLUSÃO: Familiares de pacientes celíacos apresentam autoanticorpos positivos e o acompanhamento sorológico desses indivíduos é utilizado como instrumento na identificação de doenças autoimunes ao longo dos anos.

Respuesta a la vacunación contra hepatitis B en pacientes pediátricos con enfermedad celíaca / Hepatitis B vaccination in children with celiac disease, inmunological response

Determinar la respuesta inmunológica a la vacunación contra virus de hepatitis B en pacientes pediátricos con enfermedad celíaca. Se revisaron 25 historias clínicas de celíacos diagnosticados entre 2001-2010 por estudios serológico, histopatológicos, genético y esquema de vacunación hepatitis B completo, de los cuales se excluyeron 11 pacientes. Se solicitó anticuerpo contra antígeno de superficie virus hepatitis B. El grupo de celíacos no respondedores fue evaluado posterior a revacunación bajo apego a dieta sin gluten. Se estudiaron 14 pacientes (35,7% hembras, 64,3% varones). 8 pacientes se vacunaron al nacer y 6 después de los 8 años de edad. De los cuales 28,6% tuvieron baja respuesta a la vacunación y 71,4% sin respuesta. La respuesta fue positiva en 3/8 (37,5%) de los pacientes vacunados al nacer y en 1/6 de los mayores de 8 años (16,7%). 4 no respondedores fueron revacunados cumpliendo dieta libre de gluten, evidenciándose respuesta inmunológica positiva en el 75%. Existe una disminución en la respuesta a la vacunación contra hepatitis B en pacientes celíacos, asociado a HLA DQ2 y que la dieta libre de gluten puede mejorar la respuesta inmunológica

To determine the immune response to the vaccination against hepatitis B virus in pediatric patients with celiac disease. Reviewed 25 medical histories of celiac diagnosed between 2001-2010 by serological, histopathological, genetic studies and full hepatitis B vaccination scheme, of which 11 patients were excluded. Also ask antibody against hepatitis B virus surface antigen The group of non-responder celiac was evaluated after revaccination under attachment to diet without gluten. 14 Patients were studied (35.7% females, 64.3% boys). 8 patients vaccinated at birth and 6 after eight years of age. Of which 28.6% had low response to vaccination and 71.4% unanswered. The answer was positive in 3/8 (37.5%) of patients vaccinated at birth and 1/6 of the 8 older (16.7%). not answering. 4 were fulfilling gluten-free diet, showing response immunological positive in 75%. There is a decrease in the response to vaccination against hepatitis B in celiac patients, conditional primarily by HLA DQ2 and that the gluten-free diet can improve the immune response