Prevalence of IgA anti-tissue transglutaminase antibody in a cohort of iranians patients with inflammatory bowel disease

Background and Aims: Some studies have reported the coexistence of inflammatory bowel disease (IBD) and celiac disease (CD). However, the prevalence of anti-tissue transglutaminase antibodies (IgA and IgG) and their screening value in patients with IBD is not yet clear. This study aimed to assess the prevalence of IgA anti-tTG and its potential correlation with disease status in patients with IBD. Materials and Methods: This cross-sectional study was conducted on 110 patients with confirmed IBD diagnosis at Ghaem Hospital, Mashhad, Iran. For each patient, all demographic and clinical data including age, extra intestinal manifestations, underlying diseases, types of diseases, and surgical history were collected. IgA anti-tissue transglutaminase titers were assessed by enzyme-linked immunosorbent assay. Results: None of the patients with IBD were positive for IgA anti-tTG antibodies, with a mean titer of 3.31 ± 1.3 AU/mL. Also, the mean titers were not associated with age, gender and various disease clinical features including the disease history, underlying disease, diagnosis type, extraintestinal manifestations, and surgery history. Conclusion: No significant prevalence pattern of IgA anti-tTG antibody was observed in patients with IBD. Accordingly, serological screening for CeD is not recommended in IBD patients, unless in a relevant clinical CeD suspicion. (AU)

Anticuerpos antitransglutaminasa tisular en pacientes con síntomas gastrointestinales

Introducción: La enfermedad celiaca es una enteropatía mediada por la respuesta inmune, que ha sido crecientemente reconocida como una enfermedad común, que afecta tanto a la población infantil, como a la adulta. La serología es un componente clave de la detección y diagnóstico de la celiaquía. Objetivo: Evaluar la utilidad diagnóstica de los anticuerpos antitransglutaminasa tisular en individuos con síntomas gastrointestinales crónicos. Métodos: En un estudio de corte se determinaron los anticuerpos anti-transglutaminasa tisular IgA/G en 87 pacientes adultos y pediátricos con indicación médica de anticuerpos de celiaquía. Los anti- transglutaminasa tisular IgA/G se realizaron por el ensayo inmunoadsorbente ligado a enzima y por el ensayo multiplex de inmunoblot. Se aplicó la prueba U de Mann-Whitney y se calculó el coeficiente de concordancia kappa. Resultados: La seroprevalencia de los anti-transglutaminasa tisular IgG/IgA resultó de 8,05 % (7/87) por el ensayo inmunoenzimático. Los resultados cualitativos del ensayo inmunoenzimático y del inmunoblot para los anti- transglutaminasa tisular fueron concordantes con un coeficiente kappa de 0,407 (p=0,004). La distribución de la concentración de los anticuerpos anti-TGt IgA/G obtenidos por el ensayo inmunoenzimático respecto a los resultados negativos y positivos del inmunoblot no fue significativa (p=0,08). Los pacientes con presencia de anti-transglutaminasa tisular IgA/G por el ensayo inmunoenzimático obtuvieron el diagnóstico definitivo de enfermedad celiaca confirmado por biopsia duodenal. Conclusiones: Se confirmó la utilidad de la detección de los anticuerpos anti-transglutaminasa tisular IgA/G por el ensayo inmunoenzimático como primer paso diagnóstico de la enfermedad celíaca en pacientes con síntomas gastrointestinales.

Introduction: Celiac disease is an immune-mediated enteropathy that has been increasingly recognized as a common disease, affecting both the pediatric and adult population. Serology is a key component of the detection and diagnosis of celiac disease. Objective: To evaluate the diagnostic usefulness of anti-tissue transglutaminase antibodies in individuals with chronic gastrointestinal symptoms. Methods: In a cutoff study, anti-tissue transglutaminase IgA/G antibodies were determined in 87 adult and pediatric patients with medical indication for celiac disease antibodies. Anti-tissue transglutaminase IgA/G was performed by enzyme-linked immunoadsorbent assay and multiplex immunoblot assay. Mann-Whitney U test was applied and kappa correspondence coefficient was calculated. Results: The seroprevalence of anti-tissue transglutaminase IgG/IgA was 8.05 % (7/87) by enzyme-linked immunosorbent assay. The qualitative results of the enzyme-linked immunosorbent assay and immunoblot for anti-tissue transglutaminase were consistent with a kappa coefficient of 0.407 (p=0.004). The distribution of the concentration of anti-TGt IgA/G antibodies obtained by enzyme-linked immunosorbent assay with respect to negative and positive immunoblot results was not significant (p=0.08). Patients with presence of anti-tissue transglutaminase IgA/G by enzyme-linked immunosorbent assay obtained the definitive diagnosis of celiac disease confirmed by duodenal biopsy. Conclusions: The usefulness of detection of anti-tissue transglutaminase IgA/G antibodies by enzyme-linked immunosorbent assay as a first diagnostic step of celiac disease in patients with gastrointestinal symptoms was confirmed.

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.

Short stature as a significant marker in celiac disease

Background: Celiac disease (CD) is a genetically determined gluten-sensitive enteropathy resulting in nutrient malabsorption, can have extra gastrointestinal tract (GIT) presentations, short stature may be the only presenting clinical feature, even in the absence of gastrointestinal symptoms. The aim and objective of this study was toMethods: This cross-sectional study was performed on 1000 children between ages 5 to 10 year of different schools, in Jaipur, district of Rajasthan. An anthropometric measurement (height, weight) was done for all children. Serum samples were analyze for IgA antibodies to human tissue transglutaminase (tTG) with lower detection limit of 1.0 U/ml and 15 U/ml. Positive samples for tTG antibodies were reanalyzed human endomysial autoantigens (EmA).Results: Out 1000 children screened, six were seropositive, of those four were females and two were males. The serological proportion of CD in this population was 1:166. These Six seropositive group tends to have lower height, weight than the seronegative group, but the difference was only significant for height (P=<0.01).Conclusions: Although gastrointestinal manifestations are important presentation of celiac disease, nevertheless short stature alone or in combination with other symptoms of celiac disease has been present.

Response to gluten free diet in sero-positive celiac disease children suffering from severe acute malnutrition in age group 1-5 years

Background: Diagnosis of celiac disease in children suffering from severe acute malnutrition without duodenal biopsy or HLA typing is a dilemma. The objective of this study was to study the response to gluten free diet in sero-positive Celiac Disease children suffering from severe acute malnutrition in age group 1-5 years.Methods: This prospective, observational, hospital-based study was conducted at MTC of tertiary care medical college hospital of southern Rajasthan from Dec. 2017 to Nov. 2018. Total 110 children with SAM were enrolled and screened for celiac disease on the basis of tissue tTg-IgA/IgG serology. Seropositive cases were kept on gluten free diet for short period of time and observed for the resolution of symptoms and improvement in growth, monitored by anthropometry on discharge and follow up visit.Results: Mean weight gain (gm/kg/day) on follow up was 3.87'3.49 in seropositive and 1.88'3.79 in seronegative cases (P-value<0.05). Mean weight gain was 6.43'3.28gm/kg/day in only tTg-IgA positive and 3.04'2.95 gm/kg/day in only tTg-IgG positive cases (P-value-<0.05). The mean weight gain in strictly gluten free adherent sero-positive cases was 4.89'2.97 gm/kg/day while in gluten free non-adherent patients it was -0.49'1.70 (P-value <0.001). Mean weight gain in probable (tTg-Ig-A <10 times ULN) and presumptive (tTg-IgA >10 times ULN) Celiac disease were 3.44'3.73 and 5.44'3.78, respectively without statically significant difference (P-value >0.05).Conclusions: In situations where facility of duodenal biopsy and or HLA DQ2/DQ8 typing is not available, resolution of symptoms and improvement in growth on gluten free diet confirms the diagnosis of celiac disease.

Role of anti-tissue transglutaminase IgA+IgG antibodies in detection of potential celiac disease in patients with type 1 diabetes

Background & objectives: Celiac disease (CD) can exist in various forms in type 1 diabetes (T1D) patients and can remain undetected, leading to severe complications. This study was aimed to evaluate five commercially available anti-tissue transglutaminase (tTG) ELISA kits with distinct formats for the detection of CD and potential CD in T1D patients. Clinical and demographic profiles of the patients with different disease subsets were also studied. Methods: Fifty T1D patients with classical and non-classical symptoms of CD and 100 T1D patients without any symptoms of CD were included in this study. Anti-tTG autoantibody levels were estimated by five ELISA kits followed by histological examination of duodenal biopsy. HLA DQ2-DQ8 and DRB1-DQB1 typing was done, and serum levels for transforming growth factor (TGF)-?1 were also estimated. Results: Assay format detecting anti-tTG IgA antibodies against recombinant antigens along with neopeptides of gliadin was most efficient in the detection of CD in symptomatic patients, and assay format detecting IgA+IgG helped in the detection of potential CD in asymptomatic T1D patients. These findings were supported by histological examination and human leucocyte antigen analysis. Patients with potential CD were found to have markedly deranged glycaemic control parameters and also had significantly raised serum levels of TGF-?1, (P <0.05) compared to T1D patients. Interpretation & conclusions: Potential CD can be frequently seen in T1D patients. This can be attributed to the dietary patterns prevalent in the subcontinent and the genetic basis of the disease. Anti-tTG IgA+IgG antibodies can be useful in the detection of these potential CD cases in T1D patients. Early intervention with gluten-free diet can be considered in these patients for better disease management.

Actualización en el diagnóstico de la enfermedad celiaca / An update on diagnosis of coeliac disease

La enfermedad celiaca (EC) es una afección autoinmune multisistémica inducida por el gluten en personas genéticamente susceptibles. La presentación clínica clásica es con un síndrome diarreico crónico, aunque existen formas atípicas y silentes, lo cual dificulta el diagnóstico. El mismo se basa en la detección de diversos autoanticuerpos, sobre todo la IgA contra la transglutaminasa tisular, aunque la prueba de oro es el estudio anatomopatológico de biopsias duodenales obtenidas por endoscopia digestiva alta. La ausencia del gen HLA es una prueba que se utiliza para descartar la EC. La respuesta a la dieta sin gluten confirma esta afección, que de no diagnosticarse oportunamente y tratarse en forma adecuada puede llevar a complicaciones graves.

Celiac disease (CD) is a multisystem autoimmune condition induced by gluten in genetically susceptible individuals. The classical clinical presentation is the chronic diarrhea syndrome although there are atypical and silent forms, which rnay lead to diagnostic problems. Diagnosis is based on the detection of various autoantibodies, especially against tissue transglutaminase IgA, although the gold standard is the pathological examination of duodenal biopsies obtained by upper endoscopy. The absence of the HLA gene is a test used to rule CD. The response to gluten-free diet confirms this condition, which if not promptly diagnosed and properly treated can lead to serious complications.

An analysis of clinical features of celiac disease patients in different ethnic / 中华内科杂志

Objective To summarize the clinical features of different racial patients with celiac disease (CD) and analyze the disease prevalence,diagnosis and treatment in Chinese population.Methods All the patients were diagnosed as CD and enrolled in Beijing United Family Hospital between January 2005 and July 2015.Clinical data including nationality,age,symptoms,endoscopic and pathological findings,outcome were collected and compared in patients from different countries.Results A total of 87 patients were enrolled including 63 Caucasians,18 Asian patients and 6 Middle East patients.The peak age of disease onset was 40-60 years old.Patients with typical symptoms such as chronic diarrhea and weight loss only accounted for 20.7％ (18/87) and 9.2％ (8/87) respectively.Some patients presented with nonspecific symptoms such as abdominal pain and bloating [32.2％ (28/87)],even constipation [5.7％ (5/87)].13.8％ (12/87) patients were previously diagnosed as irritable bowel syndrome.The incidence of abdominal pain,bloating,diarrhea and constipation between Asians and Caucasians had no statistical significance (P ＞ 0.05);but the proportions of weight loss,growth retardation,iron deficiency anemia and dermatitis herpetiformis in Asian group were significantly higher than that in Caucasian group (P ＜ 0.05).IgA type of anti-gliadin antibody (AGA),endomysium antibody (EMA) and tissue transglutaminase antibody (tTGA) were dominant autoimmune antibodies in patients with CD,which accounted for 58.6％ (51/87),44.8％ (39/87) and 36.8％ (32/87) respectively.The endoscopy showed that the lesion of CD was mainly located in small intestine,with reducing severity from the proximal to the distal small intestine.The lesions of duodenal bulb and descending duodenum appeared more significant in Asian group.Accordingly pathological intestinal atrophy and the degree of intraepithelial lymphocytosis were more severe in Asian patients.All 87 cases took the gluten-free diet (GFD).Eighty-one cases received serological follow up and 8 with endoscopic intestinal biopsy.The celiac disease antibodies in 47 patients turned negative from 6-9 months after GFD treatment,while 34 patients turned negative from 12-18 months after GFD.All patients reported disease remission to some extent.After 1 year GFD treatment,the pathology of endoscopic intestinal biopsy in 8 patients showed significant improvement of villous atrophy and lymphocyte infiltration.Conclusions CD patients with typical clinical manifestations are not the majority.Serological celiac disease antibodies (AGA,EMA and tTGA) have a high diagnostic value.GFD treatment is effective on majority of celiac patients.Clinical manifestations,endoscopy,intestinal pathology,and response to GFD in Chinese patients are not the same as Caucasians.Clinicians need to pay attention to the differential diagnosis.

Knockdown of tissue transglutaminase in SaOS-2 cell line inhibits its osteoblastic differentiation and mineralization / 中国实验动物学报

Objective To investigate whether TG2 plays an important role in the osteoblast differentiation and mineralization.Methods TG2 mRNA of SaOS-2 cells was knocked down using a lentivirus stably expressing short-hairpin ( sh) RNA targeting TG2.Then the cells were cultured in osteo-inductive medium for 14 d to measure mineralization and for 7 d to measure the levels of osteoblastic differentiation markers including ALP activity and mRNA of collagen I, osteocalcin ( OCN) and BMP-2.The wild-type SaOS-2 cells and scrambled shRNA-transducted SaOS-2 cells served as the controls. Results The controls displayed an increasing trend of the level of ALP activity and mRNA of collagen I, osteocalcin and BMP-2,and notable mineralization at 14 d.When TG2 was knocked down, ALP activity, mRNA of collagen I, osteocalcin and BMP-2 at 7d,and mineralization at 14 d were all significantly lower in comparison with the corresponding values in the controls.Conclusion TG2 is involved in the differentiation and mineralization of osteoblasts in vitro.

Tissue transglutaminase-interleukin-6 axis facilitates peritoneal tumor spreading and metastasis of human ovarian cancer cells / 한국실험동물학회지

Inflammation has recently been implicated in cancer formation and progression. As tissue transglutaminase (TG2) has been associated with both inflammatory signaling and tumor cell behavior, we propose that TG2 may be an important link inducing interleukin-6 (IL-6)-mediated cancer cell aggressiveness, including cancer stem cell-like characteristics and distant hematogenous metastasis. We evaluated the effect of differential TG2 and IL-6 expression on in vivo distant metastasis of human ovarian cancer cells. IL-6 production in human ovarian cancer cells was dependent on their TG2 expression levels. The size and efficiency of tumor sphere formation were correlated with TG2 expression levels and were dependent on TG2-mediated IL-6 secretion in human ovarian cancer cells. Primary tumor growth and propagation in the peritoneum and distant hematogenous metastasis into the liver and lung were also dependent on TG2 and downstream IL-6 expression levels in human ovarian cancer cells. In this report, we provide evidence that TG2 is an important link in IL-6-mediated tumor cell aggressiveness, and that TG2 and downstream IL-6 could be important mediators of distant hematogenous metastasis of human ovarian cancer cells. Intervention specific to TG2 and/or downstream IL-6 in ovarian cancer cells could provide a promising means to control tumor metastasis.

Intimal Hyperplasia in Loop-Injured Carotid Arteries Is Attenuated in Transglutaminase 2-Null Mice

Arterial restenosis frequently develops after open or endovascular surgery due to intimal hyperplasia. Since tissue transglutaminase (TG2) is known to involve in fibrosis, wound healing, and extracellular matrix remodeling, we examined the role of TG2 in the process of intimal hyperplasia using TG2-null mice. The neointimal formation was compared between TG2-null and wild-type (C57BL/6) mice by two different injury models; carotid ligation and carotid loop injury. In ligation model, there was no difference in intimal thickness between two groups. In loop injury model, intimal hyperplasia developed in both groups and the intimal/medial area ratio was significantly reduced in TG2-null mice (P = 0.007). TG2 was intensely stained in neointimal cells in 2 weeks. In situ activity of TG2 in the injured arteries steadily increased until 4 weeks compared to uninjured arteries. Taken together, intimal hyperplasia was significantly reduced in TG2-null mice, indicating that TG2 has an important role in the development of intimal hyperplasia. This suggests that TG2 may be a novel target to prevent the arterial restenosis after vascular surgery.

Celiac and Non-Celiac Forms of Gluten Sensitivity: Shifting Paradigms of an Old Disease.

Gluten sensitivity is one of the prominent features of celiac disease (CD) which is an autoimmune disorder characterized by damaged lining of the small intestine. CD was known already to ancient Greeks as κοιλιακός (keeleeakoss) i.e. disease of the abdominal cavity hence celiac. Focus of this Commentary article is on rather complex definition of CD and its emerging new forms the example of which is non-celiac gluten sensitivity. It is becoming evident that to formulate more effective treatments, these associations and newly identified disease entities deserve attention from both academic and clinical communities.

Effect and mechanism of tissue transglutaminase-mediated chemoresistance in cancer cells / 肿瘤研究与临床

TG2 is a calcium-dependent enzyme that catalyzes the formation of covalent bonds between free amine groups in one protein and protein-bound glutamines of another,creating highly cross-linked protein complexes.TG2 is ubiquitous and most diverse member of the transglutaminase family of enzymes.TG2 are implicated in cell differentiation,receptor-mediated endocytosis,cell adhesion,and induction of apoptosis.Recently,a growing body of literature suggests that it could be closely related to the development of drug resistance.Its role in cancer biology is briefly reviewed in this paper.

Prevalence of celiac disease: multicentric trial among pediatric population from five urban districts in Argentina / Prevalencia de enfermedad celíaca: estudio multicéntrico en población pediátrica de cinco distritos urbanos de la Argentina

Introduction. No published material on the preva lence of celiac disease (CD) in the pediatric population of Argentina has been found up to date. Objective. To estimate the prevalence of CD in a pediatric population (hospital-based sample) from 5 urban districts of Argentina. Methods. In a cross-sectional descriptive study, we analyzed serum samples from 2219 children, aged 3-16 years old, which had been requested for pre-surgical tests and for physical aptitude certifcates for sports in the province of Buenos Aires, and cities of Buenos Aires, Córdoba, Santa Fe and Salta. Children with a previous and accurate diagnosis of CD were also included. IgA class tissue transglu taminase antibodies were determined using serum samples, and those samples which turned out positive were also tested for IgA class endomysium an tibodies. A small intestine biopsy was proposed for those who had a positive serology. Results. Between May 2008 and August 2009, 29 positive serologies were found. A total of 22 duo denum biopsies were performed, and 21 turned out compatible with CD. Out of 2219 children, 7 had a previous diagnosis. A prevalence of 1.26% (1:79 children), with female gender predominance (p < 0.023) was found. Ninety percent of the celiac children were over 6 years old (p < 0.021). Silent celiac disease predominated but there was a 33% of symptomatic cases. Conclusions. The results of the trial show a higher prevalence of CD than expected. The finding of symptomatic patients (33%) suggests the undertak ing of different activities to spread the knowledge on this disease and promote the indication for serology test, to avoid complications by means of an early diagnosis.

Introducción. Hasta la fecha del estudio no se hallaron estudios poblacionales publicados sobre prevalencia de enfermedad celíaca en la población pediátrica argentina. Objetivo. Estimar la prevalencia de la enfermedad celíaca en población pediátrica a partir de una muestra de base hospitalaria de cinco distritos urbanos. Método. Diseño descriptivo de corte transversal. Bajo consentimiento informado, participaron 2219 niños, de 3 a 16 años, que realizaban estudios de laboratorio para exámenes prequirúrgicos o certificados de aptitud física deportiva del Conurbano bonaerense, y ciudades de Buenos Aires, Santa Fe, Córdoba y Salta. Se incluyeron niños con diagnóstico previo y certero de enfermedad celíaca dentro de esa población. Se determinaron anticuerpos antitransglutaminasa y, en las muestras positivas, anticuerpo antiendomisio. Se propuso biopsia de intestino delgado a quienes presentaron ambas serologías positivas. Resultados: 29 serologías fueron positivas. Se realizaron 22 biopsias de duodeno, 21 fueron compatibles con enfermedad celíaca y 7 presentaron diagnóstico previo. La prevalencia fue de 1,26% (1:79) IC 95% 0,84-1,81, con predominio del sexo femenino (p <0,039). El 90% de los niños celíacos hallados fueron mayores de 6 años. Las formas clínicas silentes predominaron, pero hubo un 33% de casos sintomáticos. Conclusión. Los resultados en la población estudiada muestran una prevalencia mayor que la esperada. El hallazgo de formas sintomáticas (33%) sugiere emprender acciones de difusión del conocimiento de la enfermedad y ampliar la indicación de serología para obtener diagnóstico precoz.

Refractory Coeliac Disease; Role of Nigella sativa as Immunomodulator.

Aim: The aim of this study was to assess the immunological and histological profiles of adult coeliac patients after commencing Nigella sativa (NS) oil with gluten free diet (GFD) for a period of 1 year ± 1month to prove its validity in treatment of refractory coeliac disease (CD). Methodology: Thirty two adult coeliac patients who all accepted to do endoscopy and duodenal biopsy in addition to serological assessment before and after treatment of GFD alone or with NS oil capsules for a period of 1 year ± 1 month. Duodenal biopsies were interpreted histologically according to modified Marsh criteria and the sera were tested for antigliadin antibody (AGA), anti tissue transglutaminase antibody (tTG) and endomysium antibody (EMA). Results: The response to gluten withdrawal with NS oil for a period of 1 year ± 1 month in CD patients was better than GFD alone with significant response to serological markers. Conclusion: The administration of NS oil with GFD to CD patients leads to a significant decreases more than GFD alone in the levels of all immunological parameters with histological improvement and stop the disease process (P=0.001). Ultimately, the results emerging from this study may substantially improve the immunotherapeutic application of NS in clinical management of refractory CD cases.

Expression and significance of tissue transglutaminase and VEGF in epithelial ovarian carcinoma / 中国综合临床

Objective To investigate the expression of tissue transglutaminase(tTG) and vascular endothelial growth factor(VEGF) in epithelial ovarian carcinoma and the relationship of invasion and metastance in ovarian carcinoma.Methods The expression of tTG and VEGF was detected in 55 malignant and 21 benign ovarian neoplasms by immunohistochemical SP method.The clinical significance of tTG and VEGF and their relationship were analyzed.Results The expression rates of tTG and VEGF in malignant epithelial ovarian tumors were significantly higher than in benign epithelial ovarian tumors(tTG:92.7％ vs.38.1％,x2 =32.620,P ＜0.01 ;VEGF:90.9％ vs.47.6％,x2 =19.570,P ＜0.01).In ovarian cancer,the expression of tTG in tumor cells and stromal cells was significantly related to clinical phases and the presence of ascites.The expression of VEGF in tumor cells had a significant revelance to clinical phases,pathological grades and ascites.The expression of tTG in ovarian cancer cells was positively correlated with VEGF(r =0.8856,x2 =43.14,P ＜0.01).Conclusion Tissue transglutaminase and VEGF were detected not only in tumor cells,but also instromal cells.High expression of tTG and VEGF may play an importaant role in the pathogenesis of ovarian cancer and their synergistic effect may act as an important factor in promoting the invasion and metastasis of this cancer.

Enfermedad celiaca en niños / Celiac disease in children

La enfermedad celíaca (EC) es una enteropatía autoinmune desencadenada por la ingesta de fracciones de gliadina presente en el gluten y proteínas similares del centeno y la cebada, en individuos predispuestos genéticamente. Por muchos años, la EC fue subdiagnosticada; sin embargo, dado el mayor conocimiento en su forma de presentación, junto a los nuevos test serológicos, hoy se sabe que la EC es una patología relativamente común. A pesar de que la EC puede manifestarse a cualquier edad, con un amplio espectro clínico que puede afectar cualquier órgano, los casos típicos se manifiestan en la infancia. Esta revisión pretende agrupar el conocimiento más significativo que actualmente se tiene sobre esta enfermedad.

Celiac disease (CD) is an autoimmune enteropathy triggered by ingestion of the gluten fraction of wheat proteins and similar alcohol-soluble proteins of barley and rye in genetically susceptible subjects. For many years, celiac disease has been under diagnosed. However, because of today’s greater knowledge of its presentations and the availability of new more accurate serologic tests, it is now known that CD is relatively common. Although CD can occur at any age, with a broad clinical spectrum affecting any organ, typical cases often manifest in infancy. This review aims to bring together the most significant current knowledge about this disease.

Screening children with severe short stature for celiac disease using tissue transglutaminase.

Objective. To determine the prevalence of anti-tissue transglutaminase in children and adolescents with severe short stature (<-3 SD). Methods. All children in age group of 1-18 years having height less than -3 SD for their age and sex, were included. For each child age and sex matched healthy control (height more than -2 SD) was taken. The included subjects (study & control group) were subjected to anti tissue transglutaminase (tTG) (IgA) antibody assay estimation. Results. Of the 112 cases, 23 were tTG positive, giving a prevalence of 20.5% for seropositivity among cases of short stature while all the controls were seronegative for tTG. All the 23 had tTG values above 40 U/ml and 11 had values above 100 U/ ml. On univariate analysis we found that the presence of chronic diarrhea (OR = 2.55, 95%CI - 1.08-5.98), bulky stools (OR = 3.03, 95%CI - 1.52-6.05), hemoglobin < 7 gm/dl (OR = 3.12, 95%CI - 1.55 - 6.29) and more severe short stature (<-4 SD) (OR = 0.41, 95%CI - 0.17- 0.95) had significant association with the tTG positivity. On logistic regression analysis in all cases, hemoglobin < 7gm/dl (OR = 0.090, 95%CI = 0.024-0.342) and bulky stools (OR=0.212, 95%CI = 0.069-0.649) were significantly associated with tTG positivity. Conclusion. More than one fifth of all severe short stature are seropositive for tTG and the chances of seropositivity increases if severe anemia and bulky stool are also associated.

Exactitud diagnóstica de anticuerpos antipéptidos de gliadina deamidados / Diagnostic accuracy of antibodies to deamidated gliadin peptides

El objetivo de este trabajo fue evaluar la exactitud diagnóstica de un ELISA para anticuerpos antipéptidos de gliadina deamidados en pacientes con sospecha clínica de enfermedad celíaca (EC) y comparar su rendimiento con anticuerpos antiendomisio (EMA) y antitransglutaminasa tisular (a-Tgt). Se estudiaron 169 pacientes consecutivos (16 a 79 años), sometidos recientemente a biopsia duodenal, a los cuales se les determinó anticuerpos IgA EMA, IgA a-Tgt e IgG/IgA antipéptidos de gliadina deamidados (a-DGP Screen). Sesenta y cinco pacientes tuvieron algún grado de atrofia vellositaria y probable diagnóstico de EC (11 con atrofia vellositaria parcial, 30 subtotal y 24 total) y 104 con estructura vellositaria conservada. La sensibilidad, especificidad y exactitud diagnóstica de a-DGP Screen fue de 86,2%, 98,1% y 93,5% respectivamente, similar a EMA y a-Tgt. Al considerar sólo pacientes con atrofia vellositaria subtotal y total la sensibilidad fue estadísticamente superior en los 3 ensayos (100% para a-DGP Screen, p<0,014). Se observó una excelente concordancia entre a-DGP Screen con EMA (k= 0,99) y con a-Tgt (k = 0,97). El equipo a-DGP Screen demostró una elevada exactitud diagnóstica; su rendimiento fue equivalente a EMA y a-Tgt.

The aim of this study was to evaluate the diagnostic accuracy of an ELISA for antibodies to deamidated gliadin peptides in patients clinically suspected of having celiac disease (CD), and to compare this with antibodies to endomysium (EMA) and tissue transglutaminase (a-Tgt). One hundred and sixty-nine consecutive patients (16 to 79 yo) that had recently underwent small-bowel biopsy were included; serum samples were obtained for the measurement of IgA EMA, IgA a-Tgt and IgG/IgA antideamidated gliadin peptides (a-DGP Screen) antibodies. Sixty-five patients had some degree of villous atrophy with probable diagnostic of CD (11 partial, 30 subtotal and 24 total villous atrophy); 104 individuals had normal villous architecture. The sensitivity, specificity, and accuracy of a-DGP Screen were 86.2%, 98.1% and 93.5% respectively, similar to EMA or a-Tgt. When only patients with subtotal and total villous atrophy were considered, the sensitivity was statistically higher for the 3 tests (100% for a-DGP Screen, p<0.014). An excellent agreement was observed among a-DGP Screen with EMA (κ= 0,99) and with a-Tgt (κ = 0,97). The a-DGP Screen assay showed a high diagnostic accuracy with a performance equivalent to EMA or a-Tgt.

Progress of function and mechanism of tissue transglutaminase in the process of tubulointerstitial fibrosis / 国际儿科学杂志

Tubulointerstitial fibrosis is the final common pathway of most progressive renal diseases, and also is the pathological basis that leading to chronic renal failure. In recent years, the biological effect of tissue transglutaminase in the progressive tubulointerstitium fibrosis attracts more and more attention. Tissue transglutaminase belongs to a group of calcium-dependent mammalian enzymes that have the capacity to irreversibly cross-link proteins through the formation of e (γ-glutamyl)lysine bonds, and lead to the excessive deposition of extracellular matrix, then functions markedly in the tubulointerstitial fibrosis.