Correlations of transglutaminase 2 expression in peripheral blood mononuclear cells with relevant inflammatory factors and disease severity in patients with atopic dermatitis / 中华皮肤科杂志

Objective:To determine the expression of transglutaminase 2 (TGM2) in peripheral blood mononuclear cells (PBMCs) from patients with atopic dermatitis (AD), and to analyze its correlation with AD-related inflammatory factors and disease severity.Methods:A total of 29 AD patients and 15 healthy controls were collected from the First Affiliated Hospital of Fujian Medical University from July 2020 to January 2021. Ten milliliters of peripheral blood samples were collected from each subject, so was the clinical information, including age, gender, course of disease, eosinophil counts, basophil counts, total IgE levels, Scoring AD index (SCORAD), etc. PBMCs were isolated by density gradient centrifugation. Fluorescence-based quantitative PCR was performed to determine the mRNA expression of TGM2 and AD-related inflammatory factors (interleukin [IL]-1β, IL-4, IL-6, IL-8, IL-10, IL-13, IL-17, thymic stromal lymphopoietin [TSLP], P2RX7 [purinergic receptor P2X, ligand-gated ion channel, 7], etc.) in PBMCs from 29 AD patients and 15 healthy controls, and flow cytometry to determine TGM2 protein expression on PBMCs. Mann-Whitney U test was used to analyze differences between groups, and Spearman correlation analysis to evaluate the correlation. Results:The relative mRNA expression of TGM2 in PBMCs did not differ between the AD group and control group ( M[ Q1, Q3]: 0.509 [0.325, 0.958] vs. 0.475 [0.328, 1.051], U = 210.50, P = 0.872). Compared with the control group, the AD group showed significantly decreased IL-4 mRNA expression (0.171[0.049, 0.449] vs. 0.824 [0.397, 1.378], P < 0.001), but significantly increased mRNA expression of IL-8 and IL-13 ( P = 0.011, 0.006, respectively). Spearman correlation analysis showed that the mRNA expression level of TGM2 in PBMCs was positively correlated with the mRNA expression levels of IL-4 and P2RX7 in the AD group ( rs = 0.42, 0.40, P = 0.024, 0.034, respectively), while there were no correlations between TGM2 mRNA expression and AD severity-related indicators (all P>0.05), such as age (21[16, 29] years), course of disease (4[1,10] years), eosinophil counts (0.33[0.18, 0.65] × 10 9/L), basophil counts (0.04[0.03, 0.06] × 10 9/L], SCORAD scores (60.5[46.98, 66.13] points), and serum total IgE levels (373 [40, 1 815] IU/ml). The relative protein expression levels of TGM2 on the surface of PBMCs did not differ between the AD group and control group (54.9 [47.6, 62.8] vs. 55.55 [51.5, 60.25], U = 112.00, P = 0.922) ], and no correlations were observed between the protein expression of TGM2 on PBMCs and AD severity-related indicators in the AD group (all P > 0.05) . Conclusion:No significant differences were observed in TGM2 mRNA expression in PBMCs or TGM2 protein expression on the surface of PBMCs between the AD patients and healthy controls, and there were no correlations between the TGM2 mRNA and protein expression and AD severity.

Dermatitis herpetiforme y enfermedad celíaca: del intestino a la piel / Dermatitis herpetiformis and celiac disease

Dermatitis herpetiformis is an autoimmune chronic blistering disease, considered a skin manifestation of celiac disease. Being both conditions multifactorial, they share some genetic traits and pathogenic mechanisms, which are responsible for the typical skin and gastrointestinal manifestations. In dermatitis herpetiformis, skin and other lesions heal after gluten-free diet and reappear shortly after its reintroduction to complete diet. Prevalence of celiac disease is 1% in the population, and approximately 13% of patients with the disease develop dermatitis herpetiformis. Diagnosis of celiac disease has progressively increased in recent decades, while clinical manifestations become more and more diverse. Given the current high frequency of skin lesions in celiac patients, in this review we update relevant aspects of the epidemiology, pathogenesis, clinical presentations, treatment and follow up of dermatitis herpetiformis, as a contribution to improve the management of both conditions.

Seroprevalencia poblacional de la enfermedad celiaca en zonas urbanas del Perú / Population seroprevalence of celiac disease in urban areas of Peru

RESUMEN El objetivo del estudio fue determinar la seroprevalencia de la enfermedad celiaca (EC) en zonas urbanas del Perú, utilizando una muestra de base poblacional. Se tamizó una muestra aleatoria de mujeres y varones de 18 a 29 años de 26 ciudades del Perú. Para la detección de la EC se utilizó el kit anti-transglutaminasa tisular IgA. Los resultados mayores a 20 AU/ml fueron considerados positivos. La prevalencia ponderada de la EC fue de 1,2% (IC 95%: 0,0‒2,4) y se estima que el número de personas viviendo con EC en el Perú fue de 341 783. La prevalen cia de la EC en el Perú resultó ser similar al promedio mundial.

ABSTRACT The objective of the study was to determine the seroprevalence of celiac disease (CD) in urban areas of Peru using a population-based sample. A random sample of women and men 18 to 29 years old from 26 cities in Peru was screened. An anti-tissue transglutaminase IgA kit was used for the detection of CD. Results higher than 20 AU / ml were considered positive. The weighted prevalence of celiac disease was 1.2% (CI 95%: 0.0% - 2.4%), thus the estimated number of people living with CD in Peru was 341,783. CD prevalence in Peru is similar to the world average.

Prevalence of markers of celiac disease in Colombian children with diabetes mellitus type 1 / Prevalencia de marcadores de enfermedad celíaca en niños Colombianos con diabetes mellitus tipo 1

Abstract Introduction: Although the association between diabetes mellitus type 1 (T1DM) and celiac disease (CD) is well established; there are only a few studies that focus on South American children, haplotypes and their possible associations. Objective: To determine the prevalence of CD markers in a group of children with T1DM and to analyze the associated clinical, immunological and genetic manifestations. Methods: A prevalence study focusing on children with T1DM who were assessed based on variables including sociodemographics, anthropometric information, disease characteristics, laboratory results and family medical history. In partitipants a positive tTG2 (Ig A anti-transglutaminase), a duodenal biopsy and genotype were performed. The proportion of children with T1DM and CD was estimated (CI 95%). Determinations of central tendency, univariate and bivariate analysis, were also performed; p <0.05 was considered significant. Results: Thirteen (8.4%) of the 155 children (53.6% girls, 11.0 ±3.6 years, 2-18 years) with T1DM were tTG2 positive, four had CD (2.6%), seven had potential CD (4.5%) and nine were HLA DQ2/DQ8 positive (5.8%). Children with T1DM and CD had their last ketoacidotic episode (21.5 ±30.4 months versus 69.5 ±38.8 months, p= 0.0260) earlier than children with T1DM and potential CD. There were no differences with anthropometry or with the laboratory results regarding glycemic control. Conclusions: The prevalence of CD in these children with T1DM is higher than that reported in other South American countries. The prevalence of CD was found to be associated with the time of presentation of T1DM and its main allele, the DQ2/DQ8. These findings are different from what has been described in other places around the world.

Resumen Introducción: A pesar que la asociación entre diabetes mellitus tipo 1 (DMT1) y enfermedad celíaca (EC) está bien establecida; hay pocos estudios en niños suramericanos sobre haplotipos y sus posibles asociaciones. Objetivo: Determinar la prevalencia de marcadores de EC en un grupo de niños con DMT1, analizando las manifestaciones clínicas, inmunológicas y genéticas. Métodos: Estudio de prevalencia en niños con DMT1 a quienes se les tomaron variables sociodemográficas, antropométricas, de la enfermedad, paraclínicas y familiares metabólicas. A los niños con IgA anti-transglutaminasa (tTG2) positivos, se les realizó biopsia duodenal y genotipo. Se estimó la proporción de niños con DMT1 y EC y su IC 95%; medidas de tendencia central, análisis univariado y bivariado, siendo significativa una p <0.05. Resultados: Trece (8.4%) de los 155 niños (53.6% niñas, de 11.0 ±3.6 años, 2-18 años) con DMT1 fueron tTG2 positivos, cuatro presentaron EC (2.6%), siete EC potencial (4.5%) y nueve HLA DQ2/DQ8 (5.8%). Los niños con DMT1 y EC presentaron más pronto su último episodio cetoacidótico (21.5 ±30.4 meses versus 69.5 ±38.8 meses, p= 0.0260) que los niños con DMT1 y EC potencial. No hubo diferencias con la antropometría ni con los paraclínicos del control glicémico. Conclusiones: La prevalencia de EC en estos niños con DMT1 es superior a la de otros países suramericanos; estando asociada al tiempo de presentación de la DMT1 y su principal alelo el DQ2/DQ8, hallazgos diferentes a lo descrito a nivel mundial.

Knockdown of transglutaminase-2 prevents early age-induced vascular changes in mice

Abstract Purpose: To determine whether the absence of transglutaminase 2 enzyme (TG2) in TG2 knockout mice (TG2-/-) protect them against early age-related functional and histological arterial changes. Methods: Pulse wave velocity (PWV) was measured using non-invasive Doppler and mean arterial pressure (MAP) was measured in awake mice using tail-cuff system. Thoracic aortas were excised for evaluation of endothelial dependent vasodilation (EDV) by wire myography, as well as histological analyses. Results: PWV and MAP were similar in TG2-/-mice to age-matched wild type (WT) control mice. Old WT mice exhibited a markedly attenuated EDV as compared to young WT animals. The TG2-/-young and old mice had enhanced EDV responses (p<0.01) as compared to WT mice. There was a significant increase in TG2 crosslinks by IHC in WT old group compared to Young, with no stain in the TG2-/-animals. Optical microscopy examination of Old WT mice aorta showed thinning and fragmentation of elastic laminae. Young WT mice, old and young TG2-/-mice presented regularly arranged and parallel elastic laminae of the tunica media. Conclusion: The genetic suppression of TG2 delays the age-induced endothelial dysfunction and histological modifications.

Celiac Crisis: an unusual presentation of gluten-sensitive enteropathy

Celiac disease (CD)­also known as gluten-sensitive enteropathy­is a chronic, genetically predisposing and autoimmune entity with a wide range of clinical manifestations triggered by gluten ingestion, which affects 1% of the general population. Currently, up to 60% of the diagnosis of CD is in adults due to the atypical course of the disease. The severe acute onset of CD­also called celiac crisis­is very uncommon and is still not well documented in adults. We report the case of a 58-year-old man who presented a 45-day history of subtle-onset diarrhea followed by malabsorption syndrome with progressive weight loss, anasarca, and electrolyte disturbances. The diagnostic work-up included an upper digestive endoscopy, which showed scalloping of the duodenal mucosa with pathological features confirmed on biopsies. Specific antibodies were positive, and a satisfactory clinical response was obtained once a gluten-free diet was started. Celiac crisis is a rare initial presentation of CD characterized by severe diarrhea, dehydration, weight loss, hypoproteinemia, and metabolic and electrolyte disturbances. Although rare, it should be considered in patients with apparently unexplained chronic diarrhea.

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.

Ictiose lamelar com apresentação na vida adulta: relato de caso / Ichthyosis lamellar with presentation in adult life: case report

Contexto: A ictiose lamelar é uma genodermatose rara, de herança autossômica recessiva. Pode ser causada por diferentes genes, principalmente mutação no gene TGM1 (transglutaminase 1) no cromossomo 14, e tem incidência de 1 caso em cada 200 mil nascidos vivos. A ictiose lamelar é causa de importante impacto na qualidade de vida. Relato da comunicação: Paciente do sexo feminino, 44 anos, procura atendimento médico para investigação de sintomas psiquiátricos, os quais foram avaliados. Foi afastado qualquer quadro psiquiátrico. Encaminhada à dermatologia, devido a evidente descamação lamelar disseminada, queratodermia palmoplantar, onicodistrofias e ectrópio bipalpebral. O exame clínico dermatológico e a avaliação histopatológica, evidenciaram características de ictiose lamelar, nunca tratada. Discussão: A ictiose lamelar é, na maioria das vezes, diagnosticada ao nascimento, com apresentação clínica muitas vezes sob a forma de bebê colódio. Este caso apresentou-se na vida adulta, com história desde o nascimento e, portanto, descartou-se a ictiose adquirida, relacionada a afecções nutricionais, metabólicas ou até paraneoplásicas. Conclusões: Este caso ilustra as manifestações da ictiose lamelar em paciente adulta em sua evolução natural, sem a interferência de tratamento.

Celiac Disease in Children with Moderate-to-Severe Iron-deficiency Anemia

Objective: To evaluate the proportion of children with moderate to severe iron-deficiencyanemia who have associated celiac disease. Methods: This cross-sectional analytical studywas conducted among children aged 1 to 12 years of age with moderate-to-severe irondeficiency anemia and control children without anemia.Serum IgA-tissue trans-glutaminaselevels were assessed in both cases and controls. All children with positive celiac serologyunderwent upper gastrointestinal endoscopy and duodenal biopsy; biopsy finding of Marshgrade 3 was considered positive for celiac disease. Results: There were 152 anemic childrenand 152 controls with mean (SD) hemoglobinof 7.7 (1.8) and 12.2 (0.74) g/dL, respectively.16 (10.5%) cases and 3 (2%) control patients had positive serology for celiac disease [OR(95% CI) 5.33 (1.52-18.67), P=0.007]. Six (3.9%) children with iron-deficiency anemia andnone of the controls had biopsy features diagnostic of celiac disease. Conclusion:In theNorthern Indian tertiary-care hospital outpatient setting, Celiac disease was associated with4% of children presenting with moderate-to-severe anemia.

Anti-TTG entre crianças com constipação funcional crônica não responsivas após 6 semanas de tratamento da constipação / Anti-ttg among children with chronic functional constipation unresponsive to 6 weeks of treatment of constipation

ABSTRACT BACKGROUND Celiac disease is a glutten induced enteropathy. Some authors recommended screening celiac in children with constipation. There are studies to evaluate celiac disease in children with constipation. But most of them included children regardless to treatment failure. OBJECTIVE The aim of this study was to evaluate frequency of elevated anti TTG in children with constipation after failure to improve during 6 week of appropriate treatment of constipation. METHODS In this cross sectional study, 550 children with prolonged constipation were included. Place of study was Pediatric Gastroenterology clinic of Abuzar children's hospital. Prolonged constipation was defined as a constipation which failed to resolved after 6 weeks of appropriate treatment. Constipation was defined according to ROME III criteria. After parental agreement, 5 mL of blood was obtained. Serum anti TTG level was measure using ELISA method by Orientec kit. Anti TTG>10 was considered positive if IgA was normal. SPSS version 16.0 (Chicago, IL, USA) was used for data analysis. Chi square, t-test, and Mann Whitney test used for data analysis. RESULTS In this study 550 children (m=277, f=273) were included. Mean age of the cases was 6.8±2.9 year. Anti TTG antibody level was 5.8±2.8 unit/mL. Of these case, 42 (7.6%) had positive anti-TTG antibody. Celiac disease was confirmed in 40 cases after histopathology examination. CONCLUSION Anti-TTG was positive in 7.6% children with chronic constipation who failed to respond after 6 week of treatment. Another multicenter study with longer follow up period is recommended.

RESUMO CONTEXTO A doença celíaca é uma enteropatia glúten-induzida. Alguns autores recomendam a triagem de doença celíaca em crianças com constipação. Há estudos para avaliar a doença celíaca em crianças com constipação, mas a maioria inclue crianças independentemente do insucesso do tratamento. OBJETIVO O objetivo deste estudo foi avaliar a frequência de anti-TTG elevado em crianças com constipação após 6 semanas de tratamento adequado e sem sucesso. MÉTODOS Através de cruzamento seccional, 550 crianças com constipação prolongada foram incluídas. O local de estudo foi o ambulatório de Gastroenterologia Pediátrica do Hospital Infantil de Abuzar. Constipação prolongada foi definida como uma constipação, cuja resolução falhou após 6 semanas de tratamento adequado. Constipação foi definida de acordo com critérios de Roma III. Após o consentimento informado dos pais, obteve-se 5 mL de sangue. O nível de anti TTG no soro foi medido usando-se o método ELISA pelo Orientec kit. O anti-TTG >10 foi considerado positivo se IgA estivesse normal. Os dados foram analisados através de testes do Chi-quadrado, t-teste e teste de Mann Whitney utilizando-se o SPSS versão 16.0 (Chicago, IL, EUA). RESULTADOS Um total de 550 crianças (m=277, f=273) foi incluído neste estudo. A média de idade dos pacientes foi 6,8±2,9 anos. O nível de anticorpo anti-TTG foi de 5,8±2,8 unidades/mL. Do total, 42 (7,6%) indivíduos tinham anticorpos anti-TTG positivo. A doença celíaca foi confirmada em 40 casos após exame de histopatologia. CONCLUSÃO O Anti-TTG foi positivo em 7,6% crianças com constipação crônica que não conseguiram responder após 6 semanas de tratamento. Outro estudo multicêntrico, com acompanhamento mais longo período é recomendado.

Relationship between the serum level of transglutaminase 2-specific IgE and disease condition in patients with atopic dermatitis / 中华皮肤科杂志

Objective To detect the serum level of transglutaminase 2 (TG2)-specific IgE (slgE) in patients with atopic dermatitis (AD),and to analyze its correlation with the disease condition.Methods A total of 77 patients with AD were enrolled into this study,including 44 patients aged ≥ 12 years and 33 patients aged ＜ 12 years.Of the 77 patients,20 were diagnosed with intrinsic AD,which was characterized by the absence of sIgE and total serum IgE values ＜ 150 kU/L,and 49 with extrinsic AD characterized by positive (++) or even strongly positive slgE for more than 1 kind of exogenous allergens,or total serum lgE values ≥ 150 kU/L.[mmunocapture-biotinylated detector enzyme immunoassay was performed to detect the serum level of TG2-sIgE in 77 patients with AD,40 adult patients with psoriasis vulgaris (PV) and 30 healthy adult controls.Clinical data on the AD patients were recorded,including age,disease duration,SCORAD score,blood eosinophil count,levels of total IgE and TG2-sIgE.Results The serum levels of TG2-sIgE in AD patients aged ≥ 12 years,AD patients aged ＜ 12 years,PV patients and healthy controls were 1.02 ± 0.2,1.04 ± 0.044,0.93 ± 0.25 and 0.71 ± 0.13,respectively.Additionally,the serum level of TG2-sIgE significantly differed among AD patients aged ≥ 12 years,PV patients and healthy controls (x2 =37.407,P ＜ 0.001),and was significantly higher in both AD patients aged ≥ 12 years and PV patients than in the healthy controls (t =7.38,4.83,respectively,both P ＜ 0.001).Moreover,the intrinsic AD group showed significantly higher TG2-sIgE levels compared with the extrinsic AD group (1.16 ± 0.03 vs.1.02 ± 0.20,t =2.27,P =0.02).The TG2-sIgE level was uncorrelated with the patients' age,disease duration,SCORAD score,blood eosinophil count or serum total IgE levels in AD patients (r =0.03,0.14,-0.04,-0.08,0.06,respectively,all P ＞ 0.05).Conclusion The serum level of TG2-sIgE obviously increases in AD patients,so TG2 may be one kind of autoantigen in AD patients,but there is no significant correlation between the TG2-sIgE level and AD severity.

INCREASED TISSUE TRANSGLUTAMINASE LEVELS ARE ASSOCIATED WITH INCREASED EPILEPTIFORM ACTIVITY IN ELECTROENCEPHALOGRAPHY AMONG PATIENTS WITH CELIAC DISEASE

Background - Celiac disease is an autoimmune systemic disorder in genetically predisposed individuals precipitated by gluten ingestion. Objective - In this study, we aimed to determine asymptomatic spike-and-wave findings on electroencephalography in children with celiac disease. Methods - A total of 175 children with the diagnosis of celiac disease (study group) and 99 age- and sex-matched healthy children as controls (control group) were included in the study. In order to determine the effects of gluten free diet on laboratory and electroencephalography findings, the celiac group is further subdivided into two as newly-diagnosed and formerly-diagnosed patients. Medical histories of all children and laboratory findings were all recorded and neurologic statuses were evaluated. All patients underwent a sleep and awake electroencephalography. Results - Among 175 celiac disease patients included in the study, 43 were newly diagnosed while 132 were formerly-diagnosed patients. In electroencephalography evaluation of patients the epileptiform activity was determined in 4 (9.3%) of newly diagnosed and in 2 (1.5%) of formerly diagnosed patients; on the other hand the epileptiform activity was present in only 1 (1.0%) of control cases. There was a statistically significant difference between groups in regards to the presence of epileptiform activity in electroencephalography. Pearson correlation analysis revealed that epileptiform activity in both sleep and awake electroencephalography were positively correlated with tissue transglutaminase levels (P=0.014 and P=0.019, respectively). Conclusion - We have determined an increased epileptiform activity frequency among newly-diagnosed celiac disease patients compared with formerly-diagnosed celiac disease patients and control cases. Moreover the tissue transglutaminase levels were also correlated with the presence of epileptiform activity in electroencephalography. Among newly diagnosed celiac disease patients, clinicians should be aware of this association and be alert about any neurological symptoms.

Contexto - A doença celíaca é uma doença sistêmica auto-imune em indivíduos geneticamente predispostos, precipitada pela ingestão de glúten. Objetivo - Neste estudo, tivemos como objetivo determinar achados de picos e onda assintomáticos na eletroencefalografia de crianças com doença celíaca. Métodos - Foi incluído um total de 175 crianças com o diagnóstico de doença celíaca (grupo de estudo) com idade e sexo correspondentes a 99 crianças saudáveis como controles (grupo controle) com o fim de determinar os efeitos da dieta livre de glúten nos resultados laboratoriais e na eletroencefalografia. O grupo de doença celíaca é subdividido em dois, com pacientes recém diagnosticados e anteriormente diagnosticados. Foram registrados históricos médicos e resultados laboratoriais de todas as crianças e foram avaliados os estados neurológicos. Todos os pacientes foram submetidos a um eletroencefalografia em sono e acordado. Resultados - Dos 175 pacientes com doença celíaca incluídos no estudo, 43 foram recém diagnosticados, enquanto 132 foram diagnosticados anteriormente. Na avaliação de eletroencefalografia dos pacientes a atividade epileptiforme foi determinada em 4 (9,3%) de recém diagnosticados e em 2 (1,5%) dos pacientes anteriormente diagnosticados; por outro lado, a atividade epileptiforme estava presente em apenas 1 (1,0%) dos casos de controle. Houve uma diferença estatisticamente significativa entre os grupos no que diz respeito à presença de atividade epileptiforme em eletroencefalografia. Análise de correlação de Pearson revelou que atividade epileptiforme na eletroencefalografia tanto no sono como na vigília foram positivamente correlacionados com níveis de transglutaminase tecidual (P=0,014 e P=0,019, respectivamente). Conclusão - Determinamos uma frequência de atividade epileptiforme aumentada entre pacientes recém diagnosticados com doença celíaca em comparação com pacientes anteriormente diagnosticados e casos de controle. Além disso, os níveis de transglutaminase tecidual também foram correlacionados com a presença de atividade epileptiforme na eletroencefalografia. Os clínicos devem estar cientes dessa associação e alertas sobre algum sintoma neurológico entre pacientes recentemente diagnosticados de doença celíaca.

THE PREVALENCE OF CELIAC DISEASE IN PATIENTS WITH IRON-DEFICIENCY ANEMIA IN CENTER AND SOUTH AREA OF IRAN

Background - Celiac disease is an immune-mediated enteropathy due to a permanent sensitivity to gluten in genetically susceptible people. Iron-deficiency anemia is the most widely experienced anemia in humans. Iron-deficiency anemia additionally is a common extra intestinal manifestation of celiac disease. Objective - To investigate correlation between tTg levels and histological alterations and then to determine the prevalence of celiac disease in Center and South area patients of Iran with iron deficiency anemia. Methods - A total of 402 patients aged 12-78 years who presented with iron-deficiency anemia were included in this study. Hemoglobin, mean corpuscular volume and serum ferritin were determined. Venous blood samples for anti-tissue transglutaminase antibody immunoglobuline A and G were obtained from these patients. Upper gastrointestinal endoscopy was recommended to patients who had positive serology. Results - Of 402 patients with iron-deficiency anemia, 42 (10.4%) had positive serology for celiac disease. The small intestine biopsy of all patients with positive serology showed pathological changes (Marsh I, II & III). There was not significant difference in the mean hemoglobin level between iron-deficiency anemia patients with celiac disease and without celiac disease, duodenal biopsy results did not show significant relationship between the severity of pathological changes and levels of anti-tTG IgG (P -value: 0/869) but significant relationship was discovered between pathological changes and levels of anti-tTG IgA (P -value: 0/004). Conclusion - Screening of celiac disease by anti-tissue transglutaminase antibody should be completed as a routine investigation in patients with iron-deficiency anemia. Also physicians must consider celiac disease as a possible reason of anemia in all patients with iron deficiency anemia.

Contexto - A doença celíaca é uma enteropatia imunomediada, devido a uma sensibilidade permanente ao glúten em pessoas geneticamente suscetíveis. A anemia por deficiência de ferro é a anemia mais frequente em seres humanos e, além disso, é uma manifestação extra intestinal comum da doença celíaca. Objetivo - Investigar a correlação entre níveis de imunoglobulina de anticorpos anti-transglutaminase tissular A (anti-tTG IgA) e G (IgG anti-tTG) e alterações histológicas e, em seguida, determinar a prevalência de doença celíaca no Centro e Sul do Irã em pacientes com anemia por deficiência de ferro. Métodos - Foram incluídos neste estudo um total de 402 pacientes com idades entre 12-78 anos, que apresentavam anemia por deficiência de ferro. Hemoglobina, volume corpuscular médio e ferritina sérica foram determinados. Amostras de sangue venoso para imunoglobulina de anti-tTG IgA e IgG anti-tTG foram obtidas nestes pacientes. Endoscopia gastrointestinal foi recomendada para pacientes que tiveram sorologia positiva. Resultados - Dos 402 pacientes com anemia por deficiência de ferro, 42 (10,4%) tiveram sorologia positiva para doença celíaca. A biópsia do intestino delgado de todos os pacientes com sorologia positiva mostrou alterações patológicas (Marsh I, II e III). Não houve diferença significativa no nível de hemoglobina média entre os pacientes com deficiência de ferro com ou sem a doença celíaca. O resultado da biopsia duodenal não mostrou relação significativa entre a gravidade das alterações patológicas e níveis de IgG anti-tTG (P -valor: 0/869), mas descobriu-se relação significativa entre as alterações patológicas e níveis de anti-tTG IgA (P -valor: 0/004). Conclusão - A pesquisa de doença celíaca por dosagem de anticorpo anti-transglutaminase tissular deve ser completada como investigação de rotina em pacientes com anemia por deficiência de ferro. Os clínicos devem considerar a doença celíaca como um possível causa de anemia em todos os pacientes com anemia ferropriva.

Transglutaminase 2 Expression and Its Prognostic Significance in Clear Cell Renal Cell Carcinoma

BACKGROUND: A few recent studies have demonstrated a possible role of transglutaminase 2 (TG2) in tumorigenesis or progression of renal cell carcinoma (RCC). The aim of this study was to examine TG2 expression and its clinicopathologic significance in a large number of human clear cell RCCs (CCRCCs). METHODS: We analyzed 638 CCRCC patients who underwent partial or radical nephrectomy between 1995 and 2005. The expression of TG2 was determined by immunohistochemistry and categorized into four groups, according to staining intensity: negative (0), mild (1+), moderate (2+), and strong (3+). RESULTS: TG2 staining intensity was negative in 8.5% of CCRCC (n=54), 1+ in 32.6% (n=208), 2+ in 50.5% (n=322), and 3+ in 8.5% (n=54). Strong TG2 expression was correlated with high Fuhrman nuclear grade (p=.011), high T category (p=.049), metastasis (p=.043) and male sex (p<.001) but not with N category.The survival analysis showed a significant association between strong TG2 expression and worse overall and cancer-specific survival (p=.027 and p=.010, respectively). On multivariate analysis, strong TG2 expression was a marginally significant prognostic indicator for Fuhrman nuclear grade and TNM staging (p=.054). CONCLUSIONS: Our study is the first to demonstrate the clinicopathologic significance of TG2 expression in a large number of human CCRCC samples. Strong TG2 expression was associated with high nuclear grade and poor prognosis.

Dermatitis herpetiformis: pathophysiology, clinical presentation, diagnosis and treatment

Researches on DH have shown that it is not just a bullous skin disease, but a cutaneous-intestinal disorder caused by hypersensitivity to gluten. Exposure to gluten is the starting point of an inflammatory cascade capable of forming autoantibodies that are brought to the skin, where they are deposited, culminating in the formation of skin lesions. These lesions are vesico-bullous, pruritic, and localized especially on elbows, knees and buttocks, although atypical presentations can occur. Immunofluorescence of perilesional area is considered the gold standard for diagnosis, but serological tests help in cases where it is negative. Patients who follow glutenfree diets have better control of symptoms on the skin and intestine, as well as lower risks of progression to lymphoma. Dapsone remains the main drug for treatment, but it requires monitoring of possible side effects, some potentially lethal.

Prevalence and clinical features of celiac disease in patients with autoimmune thyroiditis: cross-sectional study / Prevalência e características clínicas da doença celíaca em pacientes com tireoidite autoimune: estudo transversal

CONTEXT AND OBJECTIVE: Celiac disease is an autoimmune disorder with an average prevalence of 1% in Europe and the United States. Because of strong European ancestry in southern Brazil, this study aimed to evaluate the seroprevalence of celiac disease among autoimmune thyroiditis patients. DESIGN AND SETTING: Cross-sectional study in a public university hospital. METHODS: This cross-sectional prevalence study included autoimmune thyroiditis patients who were tested for anti-endomysial and anti-transglutaminase antibodies between August 2010 and July 2011. RESULTS: Fifty-three patients with autoimmune thyroiditis were included; 92.5% were women, with mean age of 49.0 ± 13.5 years. Five patients (9.3%) were serologically positive for celiac disease: three of them (5.6%) were reactive for anti-endomysial antibodies and two (3.7%) for anti-transglutaminase. None of them exhibited anemia and one presented diarrhea. Endoscopy was performed on two patients: one with normal histology and the other with lymphocytic infiltrate and villous atrophy. CONCLUSION: The prevalence of celiac disease among patients with autoimmune thyroid disease was 9.3%; one patient complained of diarrhea and none presented anemia. Among at-risk populations, like autoimmune thyroiditis patients, the presence of diarrhea or anemia should not be used as a criterion for indicating celiac disease investigation. This must be done for all autoimmune thyroiditis patients because of its high prevalence. .

CONTEXTO E OBJETIVO: A doença celíaca é uma doença autoimune, com prevalência média de 1% na Europa e nos Estados Unidos. Em função da forte ascendência europeia no sul do Brasil, este estudo objetiva relatar a soroprevalência de doença celíaca em indivíduos com tireoidite autoimune. TIPO DE ESTUDO E LOCAL: Estudo transversal em um hospital público universitário. MÉTODOS: Este estudo transversal de prevalência incluiu pacientes com tireoidite autoimune que foram submetidos a testes de anticorpos antiendomísio e antitransglutaminase entre agosto de 2010 e julho de 2011. RESULTADOS: Foram incluídos 53 pacientes com tireoidite autoimune, 92,5% mulheres, com idade média de 49,0 ± 13,5 anos. Cinco (9,3%) pacientes apresentaram sorologia positiva para doença celíaca, sendo três (5,6%) com anticorpo antiendomísio positivo e dois (3,7%) com antitransglutaminase positivo. Nenhum paciente apresentou anemia e um apresentou diarreia. Apenas dois pacientes realizaram endoscopia: um com histologia normal e outro apresentou infiltrado linfocitário e atrofia vilositária. CONCLUSÕES: A prevalência de doença celíaca entre pacientes com doença autoimune da tireoide foi de 9,3%; um paciente queixou-se de diarreia e ninguém apresentou anemia. Em populações de risco, como é o caso de pacientes com tireoidite autoimune, a presença de diarreia ou anemia não devem ser utilizados como critério para indicar investigação de doença celíaca, que deve ser feita em todos os indivíduos com tireoidite autoimune devido a sua alta prevalência. .

A Novel Therapeutic Target in Inflammatory Uveitis: Transglutaminase 2 Inhibitor

PURPOSE: Our goal was to investigate the effects of inhibition of transglutaminase 2 (TGase 2) on endotoxin-induced uveitis (EIU) METHODS: EIU was induced in female Lewis rats by single footpad injections of 200 microgram of lipopolysaccharide (LPS). TGase 2 inhibitors were administered intraperitoneally 30 minutes before and at the time of LPS administration. Rats were sacrificed 24 hours after injection, and the effects of the TGase 2 inhibitors were evaluated by the number of intraocular inflammatory cells present on histologic sections and by measuring the TGase 2 activity and TGase products in the aqueous humor (AqH). TGase 2 substrates were also assayed in AqH from uveitis patients. RESULTS: Clinical indications of EIU, the number of cells present on histologic sections, and TGase 2 activity in AqH increased in a time-dependent manner, peaking 24 hours after LPS injection. Inflammation in EIU was significantly reversed by treatment with TGase inhibitors. A 23-kDa cross-linked TGase substrate was identified in the AqH from EIU rats and uveitis patients. MALDI-TOF analysis showed that this substrate in uveitis patients was human Ig kappa chain C region. CONCLUSIONS: TGase 2 activity and its catalytic product were increased in the AqH of EIU rats. TGase 2 inhibition attenuated the degree of inflammation in EIU. Safe and stable TGase inhibitors may have great potential for the treatment of inflammatory uveitis.

Triagem sorológica de familiares de pacientes com doença celíaca: anticorpos anti-endomísio, antitransglutaminase ou ambos? / Serological screening of relatives of celiac disease patients: antiendomysium antibodies, anti-tissue transglutaminase or both?

RACIONAL: A doença celíaca representa, na atualidade, a doença intestinal mais comum em populações caucasóides e apresenta prevalência que varia de 8 por cento a 18 por cento nos familiares dos pacientes. A pesquisa dos anticorpos anti-endomísio (EmA-IgA) e antitransglutaminase tecidual (anti-tTG-IgA) constitui importante recurso não-invasivo e sensível de triagem e diagnóstico da doença celíaca em grupos de risco e populações. OBJETIVO: Avaliar a prevalência do EmA e anti-tTG em um grupo de familiares de celíacos e verificar o grau de concordância entre os dois métodos. MÉTODOS: Foram estudados 177 familiares (76(feminino); 101(masculino); 2-79 anos) e 93 indivíduos voluntßrios e sadios (34 (feminino); 59 (masculino); 2-71 anos) como grupo controle. O EmA foi detectado por imunofluorescência indireta (substrato: cordão umbilical humano) e o anti-tTG pelo método de ELISA (kit comercial). RESULTADOS: A positividade total de anticorpos nos familiares em estudo foi de 21 por cento (37/177), mostrando significativa diferença em relação aos controles (0 por cento; 0/93). Doze por cento (21/177) dos familiares foram positivos para o EmA e 13,56 por cento (24/177) para o anti-tTG, sendo 4,52 por cento (8/177) positivos concomitantemente para os dois anticorpos. A concordância de resultados entre os dois métodos foi de 83,6 por cento (148/177) e a discordância de 16,4 por cento (29/177), caracterizando uma correlação positiva significante (r= 0.435) entre ambos. Dentre os concordantes, 79,1 por cento (140/177) eram negativos para o anti-tTG e EmA, e 4,52 por cento (8/177) positivos para ambos. Nos casos discordantes, 7,34 por cento (13/177) apresentaram EmA positivo e anti-tTG negativo e 9,04 por cento (16/177) eram anti-tTG positivo e EmA negativo. CONCLUSÃO: Embora a alta positividade obtida para o EmA e anti-tTG destaque a importância da triagem sorológica em familiares de pacientes com doença celíaca, as discordâncias detectadas no estudo...

BACKGROUND: Celiac disease is the most common intestinal disorder of caucasian populations and presents a prevalence of 8 percent to 18 percent between the relatives of patients. The anti-endomysial (IgA-EmA) and anti-tissue transglutaminase antibodies (IgA-tTG) have represented an important non invasive and sensitivity method of screening and diagnosis of celiac disease in risk groups and populations. AIM: To investigate the prevalence of IgA-EmA and IgA-tTG antibodies in relatives of celiac patients and verify the degree of concordance between them. METHODS: One hundred and seventy seven relatives of celiac patients (76(feminino); 101(masculino); 2-79 years) and 93 healthy individuals were evaluated (34(feminino); 59(masculino); 2-71 years). IgA-EmA were detected by indirect immunofluorescence, with human umbilical cord as substrate, while anti-IgA-tTG titers were measured by enzyme-linked immunosorbent assay (ELISA), using commercial kit. RESULTS: Total positivity to antibodies in relatives of celiac patients was of 21 percent (37/177), and showed significant difference compared to control group (0 percent; 0/93). Twelve percent (21/177) of celiac disease relatives were positive to IgA-EmA, 13.56 percent (24/177) to IgA-tTG, and 4.52 percent (8/177) to both assays simultaneously. The concordance between both methods was 83.6 percent (148/177) and the discordance was 16.4 percent (29/177), with a positive and significant correlation (r = 0.435). Among the concordant results, 79.1 percent (140/177) were negative and 4.52 percent (8/177) were positive to both antibodies. Among the discordant results, 7.34 percent (13/177) were positive to IgA-EmA and negative to IgA-tTG, while 9.04 percent (16/177) were negative to IgA- EmA and positive to IgA-tTG. CONCLUSION: Although the high positivity to IgA-EmA and IgA-tTG emphasizes the importance of the serological screening in relatives of celiac patients, the discordances detected in this study...

Role of crosslinked protein in lung injury following total body irradiation and bone marrow transplantation

The aberrant protein crosslinks formation during lung injury as results total body irradiation (TBI) and bone marrow transplantation (BMT) therapy has been examined as apossible contributory factor in organ or tissue pathogenesis. Female C3HeB/ FeJ mice were used for an experimental animal. Carbon monoxide uptake (V(CO)) was measured at 1, 2, 3, 4 and 5 months after TBI at respective doses of 12, 14, 16 and 18 Gy 16 h prior to syngeneic BMT. Also as a measure of aberrant protein crosslinking in the inured tissues, transglutaminase (TGase)-activities and crosslinked protein were examined along with thrombin, a protease known to activate TGases. Reductions of VCO were detected following TBI and BMT. Activities of thrombin and TGase 1, and crosslinked protein in bronchoalveolar lavage (BAL) fluid of the mice 1 wk after TBI at 12 Gy and BMT were identified and found to be elevated in the treated animals. These findings suggest that elevated levels of crosslinked proteins and TGase I in the bronchoalveolar larvage during the lung injury could have enhanced the organ pathogenesis following TBI and BMT.

A Nonsense Mutation in Transglutaminase1Gene and Loss of Enzyme Activity in a Family with Lamellar Ichthyosis / 中华皮肤科杂志

Objective To detect the activity of transglutaminase1(TGM1)and gene mutation in a family with lamellar ichthyosis.Methods Immunohistochemistry technique was used to detect the activity of transglutaminase1.Complete encoding sequences of TGM1gene were analyzed in this family by using PCR-DNA sequencing.Results No activity of transglutaminase1was detected in the proband's skin.A nonsense mutation of C604T located in exon4of TGM1gene was identified by PCR-DNA sequencing,which caused a premature termination of Q202X and a defective polypeptide truncated by615amino acids in C-terminus.A heterozygous C604T mutation was carried by both of the proband' s parents.Conclusions The proband of lamellar ichthyosis in this family shows loss of transglutaminase1activity,which is resulted from a truncated transglutaminase1coded by the homozygous mutant TGM1gene.