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)

Gastrointestinal tract involvement in patients with potential celiac disease beyond the small intestine: An early proof with IgA anti-tissue transglutaminase-2 antibody deposits

Background: IgA anti-tissue transglutaminase-2 antibody (anti-TG2Ab) deposits in intestinal and extraintestinal organs have been used to link the respective pathological changes in these organs with celiac disease (CeD). Aims: To know if parts of intestine other than the duodenum, such as esophagus, stomach, and colon, have any pathology related to potential CeD or have mucosal IgA anti-TG2 Ab deposits. Settings and Design: A prospective case–control study conducted from April 2018 to December 2019. Materials and Methods: Nine patients with potential CeD and 27 age- and gender-matched patients with irritable bowel syndrome were recruited as cases and controls, respectively. Mucosal biopsies were collected from esophagus, stomach, duodenum, and rectosigmoid regions, histological changes were evaluated, and IgA anti-TG2 Ab deposits were analyzed in these regions by two-color immunohistochemical staining. Statistics: Data were analyzed using statistical software Stata 14.0. Results: No distinct difference in mucosal lymphocytosis were identified between biopsies of patients with potential CeD and controls at the following sites: esophagus (11.1% vs 0%, P = 0.079), stomach (14.3% vs 7.7%, P = 0.590), and rectum (20% vs 0%, P = 0.067). Co-localized IgA anti-TG2Ab deposits were observed more in potential CeD than in controls at esophagus 22.2% (2/9) vs 0%, P = 0.012; stomach 66.7% (6/9) vs 11.5% (3/26), P < 0.001; and duodenum 66.7% (6/9) vs 0%, P < 0.001 but not at rectum 0% (0/4) vs 0% (0/25). Conclusion: Although histological changes are not distinct, a subset of subjects with potential CeD has pan-intestinal involvement other than in the duodenum.

Research progress of metformin in the pathogenesis of pulmonary fibrosis / 中国临床药理学与治疗学

Pulmonary fibrosis is a chronic, progressive and irreversible respiratory disease characterized by hyperposition of extracellular matrix leading to inflammation and extensive lung remodeling. There is currently no effective treatment. Multiple studies have shown that metformin is a classic antiglycemic drug with antifibrotic potential. However, at present, there is no consensus on the specific mechanism of metformin's anti-fibrosis effect, and this paper reviews the research progress of metformin in the field of pulmonary fibrosis in recent years, mainly from IGF-1/IGF-1R/PI3K signaling, AMPK/mTOR signaling, TGF-β/Smad signaling pathway, and intervening in myofibroblast proliferation and apoptosis, improving oxidative stress, inhibiting epithelial interstitial transformation and transglutaminase. In order to be able to more deeply and comprehensively understand the antifibrosis mechanism and clinical application scope of metformin in the future, and provide new ideas for the treatment of pulmonary fibrosis.

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.

HLA DQ2/DQ8 haplotypes and anti-transglutaminase antibodies as celiac disease markers in a pediatric population with type 1 diabetes mellitus

ABSTRACT Objectives: Evaluate the celiac disease (CD) markers, within the scope of its screening, in a pediatric population with diagnosis of type 1 diabetes (T1D) at Hospital de Braga (HB) and determine the prevalence of CD in the sample. Reflect on CD screening algorithm applied in this pediatric population. Subjects and methods: Retrospective observational study with 94 patients diagnosed with T1D at age 10 years or younger, followed up at the HB Outpatient Diabetology Consultation, including those referred from other hospitals. Record of clinical information, IgA anti-transglutaminase and anti-endomysium and HLA DQ2/DQ8 haplotypes. Results: We obtained positive serological test for CD in 4 patients. This test had 100% sensitivity and specificity. The prevalence of CD was 4.3% (n = 4). Positive HLA screening in 84.6% of patients, with both sensitivity and negative predictive value of 100% and specificity of 16.67%. Diagnosis of CD was made on average 3.40 ± 3.32 years after the diagnosis of TD1. All cases of CD registered non-gastrointestinal manifestations, none had gastrointestinal symptoms. Conclusion: This study proved that there is a higher prevalence of CD in pediatric population with TD1, when compared to general population, and clarified the importance of CD screening. Furthermore, it was observed that serological screening for CD antibodies is an excellent screening test and HLA typing, although not the most suitable first line test, can be useful in excluding the possibility of patients with T1D developing CD.

Evaluation of nuclear NF-κB, transglutaminase2, and ERCC1 as predictors of platinum resistance in testicular tumors

ABSTRACT Purpose: Testicular germ cells tumor (TGCT) are associated with a high cure rate and are treated with platinum-based chemotherapy. However, a group of testicular cancer patients may have a very unfavorable evolution and insensitivity to the main therapeutic agent chemotherapy (CT) cisplatin. The aim of this study was to evaluate the risk of recurrence and overall survival related to the expression of nuclear factor kappa-B (NF-κB), transglutaminase 2 (TG2) and excision repair cross-complementation group 1 (ERCC1) in patients with TGCT treated with platinum combinations. Patients and Methods: A retrospective study was performed with TGCT patients treated with platinum-based chemotherapy. Immunohistochemical analysis was performed and the expression was correlated with clinical and laboratory data. Results: Fifty patients were included, the mean age was 28.4 years (18 to 45), and 76% were non-seminoma. All patients were treated with standard cisplatin, etoposide and bleomycin or cisplatin, and etoposide. Patient's analyzed immunodetection for NF-κB, TG2, and ERCC1 were positive in 76%, 54% and 42%, respectively. Multivariate analysis identified that positive expressions to ERCC1 and NF-κB are independent risk factors for higher recurrence TGCT after chemotherapy (RR 2.96 and 3.16, respectively). Patients with positive expression of ERCC1 presented a poor overall survival rate for 10-year follow (p=0.001). Conclusions: The expression of ERCC1 and NF-κB give a worse prognosis for relapse, and only ERCC1 had an influence on the overall survival of TGCT patients treated with platinum-based chemotherapy. These may represent markers that predict poor clinical outcome and response to cisplatin.

Enfermedad celiaca silente en pacientes adultos con enfermedades tiroideas / Silent celiac disease in adult patients with autoimmune thyroid diseases

Introducción: la enfermedad celiaca puede estar asociada en forma silente a las tiroiditis autoinmunes. Objetivo: determinar la presencia de enfermedad celiaca silente en pacientes con tiroiditis autoinmunes. Metodología: estudio observacional, prospectivo, multicéntrico realizado en pacientes adultos con tiroiditis de Hashimoto y enfermedad de Graves de tres centros hospitalarios de Paraguay en años 2018-2019. Se determinó la presencia anticuerpos IgA antitransglutaminasa e IgA sérica en aquellos que aceptaron participar del estudio. Se midieron además variables demográficas y clínicas. El estudio fue aprobado por el Comité de Ética de la Universidad Nacional de Itapúa.Resultados: se contactaron 87 pacientes, pero la muestra final estuvo constituida por 22 sujetos. La edad media fue 50 años, con predominio del sexo femenino (77%). Se detectaron anticuerpos para enfermedad celiaca en 3 casos (13%) y todos fueron confirmados con biopsia duodenal. Conclusiones: la frecuencia de enfermedad celiaca silente en pacientes con tiroiditis de Hashimoto y enfermedad de Graves fue 13%.

Introduction: celiac disease may be asymptomatically associated with autoimmune thyroiditis.Objective: to determine the presence of silent celiac disease in patients with autoimmune thyroiditis.Methodology: we carried out a observational, prospective, multicenter study in adult patients with Hashimoto's thyroiditis and Graves' disease from three hospitals in Paraguay in the years 2018-2019. The presence of IgA antitransglutaminase and serum IgA antibodies was determined in those who agreed to participate in the study. Demographic and clinical variables were also measured. The study was approved by the Ethics Committee of the National University of Itapúa. Results: 87 patients were contacted, but the final sample was established with 22 subjects. The mean age was 50 years, with a predominance of the female (77%). Antibodies to celiac disease were detected in 3 cases (13%) and all were confirmed with a duodenal biopsy. Conclusions: the frequency of silent celiac disease in patients with Hashimoto's thyroiditis and Graves' disease was 13%.

Ictiosis Lamelar autosómica recesiva: revisión de la literatura y caso clínico / Autosomal recessive lamellar ichthyosis: review of the literature and clinical case

Resumen Las ictiosis congénitas autosómicas recesivas (ICAR) son poco frecuentes a nivel mundial con una incidencia de 1:300,000 nacimientos, se caracterizan por trastornos de la queratinización, entre sus variantes engloban las formas no sindrómicas de ictiosis, como la ictiosis laminar (IL), la eritrodermiaictiosiforme congénita (EIC) y actualmente se incluyen la ictiosis arlequín, el bebé colodión autorresolutivo, el bebé colodión autorresolutivoacral y la ictiosis en traje de baño. Desde el punto de vista genético son heterogéneas, originadas por una mutación en el gen de la transglutaminasa 1 y se las haasociado a TGM1, ALOXE3, ALOX12B, NIPAL4, CYP4F22 y ABCA12. Clínicamente, la ictiosis se caracteriza principalmente por piel gruesa, escamas laminares adherentes con hendiduras profundas. En este trabajo pretende revisar los conocimientos actuales en el campo de las ICAR, incluyendo aspectos clínicos, histológicos, ultraestructurales, genético-moleculares, tratamiento,y también su manejo clínico.

Abstract The autosomal recessive congenital ichthyosis (ARCI) is a rare worldwide condition with an incidence of (1: 300,000 births), characterized by disorders of keratinization, among its variants encompass the non-syndromic forms of ichthyosis, such as laminar ichthyosis (IL) , congenital ichthyosiform erythroderma (EIC) and currently include harlequin ichthyosis, self-healing colodion baby, acral self-healing colodion baby and ichthyosis in swimsuits. From a genetic point of view, they're heterogeneous, originated by a mutation in the gene of transglutaminase 1 and associated with TGM1, ALOXE3, ALOX12B, NIPAL4, CYP4F22 and ABCA12. Clinically, ichthyosis is mainly characterized by thick skin, adherent lamellar scales with deep clefts. The aim of this work is to review the current knowledge in the field of ICAR, including clinical, histological, ultrastructural, genetic-molecular and therapeutic aspects as well as its clinical management.

Niveles de calprotectina fecal en pacientes con anticuerpos anti-transglutaminasa positivos y pacientes con dieta libre de gluten / Fecal calprotectin levels in patients with positive anti-transglutaminase antibodies and patients on a gluten free diet / Niveis de calprotectina fecal em pacientes com anticorpos anti-transglutaminase positivos e pacientes com dieta livre de gluten

La calprotectina fecal se ha afianzado en los últimos años como un marcador útil de las patologías gastrointestinales. El objetivo de este estudio fue determinar los niveles de calprotectina fecal (CPF), interleuquina-6 (IL-6) y proteína C reactiva (PCR) en tres grupos de pacientes: con diagnóstico de novo de enfermedad celíaca, con diagnóstico previo y dieta libre de gluten (DLG) y un grupo control. Se colectaron muestras de 79 pacientes entre 18 y 65 años. A todos se les determinó CPF, IL-6 y PCR como marcadores de inflamación y anticuerpos anti-transglutaminasa IgA y anti-gliadinas desaminadas IgA e IgG como marcadores serológicos. Se encontraron valores significativamente incrementados de PCR en el grupo de novo (124,06 μg/g) comparados con el grupo con DLG (23,61 μg/g) y el grupo control (16,91 μg/g) respectivamente. No se encontraron diferencias entre el grupo con DLG y el negativo (control). Idéntico comportamiento se observó para IL-6 con valores en el grupo de novo de 2,39 μg/dL, 1,74 μg/dL en el grupo con DLG y 1,41 μg/dL en el control negativo. No se encontraron diferencias significativas en el análisis de resultados de PCR. Se encontró una excelente sensibilidad (98,0%) y especificidad (96,6%) en la capacidad de la CPF para diferenciar valores de anti-transglutaminasa IgA superiores o inferiores al punto de corte cuando se estimó el índice de Youden. Se podría considerar a la CPF como un posible marcador sensible para indicar inflamación intestinal de manera no invasiva en la enfermedad celíaca.

The determination of fecal calprotectin has been strengthened in recent years as a useful marker of gastrointestinal pathologies. The objective of this study was to determine the levels of fecal calprotectin (FCP), interleukin-6 (IL-6) and C-reactive protein (CRP) in three groups of patients: with de novo diagnosis of celiac disease, with previous diagnosis and gluten-free diet (GFD) and a control group. Samples were collected from 79 patients between 18 and 65 years old. In all cases, FCP, IL-6 and RCP were determined as markers of inflammation and anti-transglutaminase IgA and deaminated anti-gliadin IgA and IgG antibodies as serological markers. Significantly more increased FCP values were found in the de novo group (124.06 μg/g) than in the group with DLG (23.61 μg/g) and the control group (16.91 μg/g). No differences were found between the group with GFD and the negative. The same trend was observed for IL-6 with values in the de novo group of 2.39 μg/dL, 1.74 μg/dL in the group with gluten free diet and 1.41 μg/dL in the negative control. No significant differences were found in the analysis of RCP results. Excellent sensitivity (98.0%) and specificity (96.6%) were found in the capability of the FCP to differentiate anti-transglutaminase IgA values higher or lower than the cut-off point when the Youden index was estimated. The FCP could be considered as a possible sensitive marker to indicate intestinal inflammation in a non-invasive manner in celiac disease.

A calprotectina fecal se consolidou nos ultimos anos como um marcador util das patologias gastrointestinais. O objetivo deste estudo foi determinar os niveis de calprotectina fecal (CPF), interleucina-6 (IL-6) e proteina C-reativa (PCR) em tres grupos de pacientes; com diagnostico de novo de doenca celiaca, com diagnostico previo e dieta livre de gluten (DLG) e um grupo controle. Foram coletadas amostras de 79 pacientes entre 18 e 65 anos. Em todos os casos CPF, IL-6 e PCR foram determinadas como marcadores de inflamacao e anticorpos anti-transglutaminase IgA e anti-gliadinas desaminadas IgA e IgG como marcadores sorologicos. Valores significantemente mais altos de PCR foram detectados no grupo de novo (124,06 μg/g) comparados com o grupo com DLG (23,61 μg/g) e o grupo controle (16,91 μg/g) respectivamente. Nao foram encontradas diferencas entre o grupo com DLG e o negativo (controle). O mesmo comportamento foi observado para IL-6 com valores no grupo de novo de 2,39 μg/dL, 1,74 μg/dL no grupo com DLG e 1,41 μg/dL no controle negativo. Na analise de resultados da PCR nao foram encontradas diferencas significativas. Foram detectadas uma sensibilidade excelente (98,0%) e especificidade (96,6%) na habilidade da CPF para diferenciar valores de anti-transglutaminase IgA superiores ou inferiores ao ponto de corte quando o indice de Youden foi estimado. Poderia ser considerada a CPF como um possivel marcador sensivel para identificar inflamacao intestinal de forma nao invasiva na doenca celiaca.

Site-specific monoPEGylated interferon alpha2a mediated by microbial transglutaminase / 生物工程学报

PEGylation is considered one of the most successful techniques to improve the characteristics of protein drugs including to increase the circulating half-life of proteins in blood and to decrease their immunogenicity and antigenicity. One known PEG modification method is to attach PEG to the free amino group, typically at lysine residues or at the N-terminal amino acid with no selectivity, resulting in a heterogeneous product mixture. This lack of selectivity can present problems when a therapeutic PEGylated protein is being developed, because predictability of activity and manufacturing reproducibility are needed for regulatory approval. Enzymatic PEGylation of proteins is one route to overcome this limitation. Transglutaminases (TGase) are enzyme candidates for site-specific PEGylation. We use human interferon alpha 2a (IFN α2a) as a test case, and predict that the potential modification residues are Gln101 by computational approach as it contains 12 potential PEGylation sites. IFN α2a was PEGylated by Y shaped PEG40k-NH2 mediated by microbial transglutaminase. Our results show that the microbial transglutaminase mediated PEGylation of IFN α2a was site-specific only at the site of Gln101 in IFN α2a, yielding the single mono-conjugate PEG-Gln101-IFN α2a with a mass of 59 374.66 Da. Circular dichroism studies showed that PEG-Gln101-IFN α2a preserved the same secondary structures as native IFN α2a. As expected, the bioactivity and pharmacokinetic profile in rats of PEG-Gln101-IFN α2a revealed a significant improvement to unmodified IFN α2a, and better than PEGASYS.

Impact of gene dosage on recombinant transglutaminase production of Pichia pastoris / 生物工程学报

Based on the rDNA sequence of Pichia pastoris, a multi-copy gene expression vector of transglutaminase (pPICZα-rDNA-mtg) was constructed and transformed to the host strain (pGAP9-pro/GS115) expressing pro peptide, to obtain the co-expression strain pro/rDNA-mtg (GS115). Real-time fluorescence quantitative PCR (qPCR) was used to analyze transglutaminase gene copy number in the 4 positive strains. We further studied the effect of gene copy on the enzyme production of recombinant Pichia pastoris as well as high-density fermentation of higher expression strain in a 3-L fermenter. The mtg copy numbers of the 4 positive strains were 2.21, 3.36, 5.72 and 7.62 (mtg-2c, mtg-3c, mtg-6c and mtg-8c), respectively, and the enzyme production capacity and protein expression level were mtg-3c>mtg-2c>mtg-6c>mtg-8c. Mtg-3c and mtg-6c of high-density fermentation had the highest enzymatic activity and enzymatic activity per unit wet weight in the supernatant of 3.12 U/mL, 52.1 U/g (wet weight) and 2.07 U/mL and 36.5 U/g (wet weight), respectively. In terms of enzyme activity per unit wet weight, mtg-3c is 1.4 times higher than that of mtg-6c. The activity of purified enzyme (mtg-3c) was up to 7.21 U/mL and the protein concentration was 437.2 μg/mL. By analyzing the effect of mtg copy number on the enzyme production of recombinant strains, mtg-3c is suitable for the co-expression of two genes (pro and mtg) in pro/rDNA-mtg, and its enzyme activity is related to higher protein secretion of the strain.

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.

Collodion Baby With Congenital Bilateral Ectropion And Eclabion- Rare Presentation

Congenital Ichthyosiform Erythroderma- an extremely rare dermatological condition with an estimated incidenceof 1 in 50,000 to 100,000 birth. There is defective Stratum corneum barrier associated with collodion membranewhen the baby moves from an amniotic fluid to external dry environment during parturition. The membranedessicates and peels off. This condition is due to mutations in Transglutaminase1, ALOX genes, ABCA12, Ichthyin,ABHD5.

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.

Transglutaminase 2 Promotes Autophagy by LC3 Induction through p53 Depletion in Cancer Cell

Transglutaminase 2 (TGase 2) plays a key role in p53 regulation, depleting p53 tumor suppressor through autophagy in renal cell carcinoma. We found that microtubule-associated protein 1A/1B-light chain 3 (LC3), a hallmark of autophagy, were tightly associated with the level of TGase 2 in cancer cells. TGase 2 overexpression increased LC3 levels, and TGase 2 knockdown decreased LC3 levels in cancer cells. Transcript abundance of LC3 was inversely correlated with level of wild type p53. TGase 2 knockdown using siRNA, or TGase 2 inhibition using GK921 significantly reduced autophagy through reduction of LC3 transcription, which was followed by restoration of p53 levels in cancer cells. TGase 2 overexpression promoted the autophagy process by LC3 induction, which was correlated with p53 depletion in cancer cells. Rapamycin-resistant cancer cells also showed higher expression of LC3 compared to the rapamycin-sensitive cancer cells, which was tightly correlated with TGase 2 levels. TGase 2 knockdown or TGase 2 inhibition sensitized rapamycin-resistant cancer cells to drug treatment. In summary, TGase 2 induces drug resistance by potentiating autophagy through LC3 induction via p53 regulation in cancer.

Urinary transglutaminase 2 as a potent biomarker to predict interstitial fibrosis and tubular atrophy of kidney allograft during early posttransplant period in deceased donor kidney transplantation

PURPOSE: Transglutaminase type 2 (TG2) is an extracellular matrix crosslinking enzyme with a pivotal role in kidney fibrosis. We tested whether quantification of urinary TG2 may represent a noninvasive method to estimate the severity of kidney allograft fibrosis. METHODS: We prospectively collected urine specimens from 18 deceased donor kidney transplant recipients at 1-day, 7-day, 1-month, 3-month, and 6-month posttransplant. In addition, kidney allograft tissue specimens at 0-day and 6-month posttransplant were sampled to analyze the correlation of urinary TG2 and kidney allograft fibrosis. RESULTS: Thirteen recipients had increased interstitial fibrosis and tubular atrophy (IFTA) scores at the 6-month protocol biopsy (IFTA group). The mean level of urinary TG2 in the IFTA group was higher compared to that of 5 other recipients without IFTA (no IFTA group). Conversely, the mean level of urinary syndecan-4 in the IFTA group was lower than levels in patients without IFTA. In the IFTA group, double immunofluorescent staining revealed that TG2 intensity was significantly upregulated and colocalizations of TG2/heparin sulfate proteoglycan and nuclear syndecan-4 were prominent, usually around tubular structures. CONCLUSION: Urinary TG2 in early posttransplant periods is a potent biomarker for kidney allograft inflammation or fibrosis.

Tissue Transglutaminase Antibody and Its Association with Duodenal Biopsy in Diagnosis of Pediatric Celiac Disease / 대한소아소화기영양학회지

PURPOSE: This study aimed to evaluate a possible association between the anti-tissue transglutaminase antibody (anti-tTG) titer and stage of duodenal mucosal damage and assess a possible cut-off value of anti-tTG at which celiac disease (CD) may be diagnosed in children in conjunction with clinical judgment. METHODS: This observational study was conducted at a gastroenterology clinic in a tertiary hospital from April 2012 to May 2013. Seventy children between 6-months and 18-years-old with suspected CD underwent celiac serology and duodenal biopsy. Statistical analyses were done using SPSS 16. Diagnostic test values were determined for comparing the anti-tTG titer with duodenal biopsy. An analysis of variance and Tukey-Kramer tests were performed for comparing the means between groups. A receiver operating characteristics curve was plotted to determine various cut-off values of anti-tTG. RESULTS: The mean antibody titer increased with severity of Marsh staging (p<0.001). An immunoglobulin (Ig) A-tTG value at 115 AU/mL had 76% sensitivity and 100% specificity with a 100% positive predictive value (PPV) and 17% negative predictive value (NPV) for diagnosis of CD (p<0.001, 95% confidence interval [CI], 0.75–1). CONCLUSION: There is an association between the anti-tTG titer and stage of duodenal mucosal injury in children with CD. An anti-tTG value of 115 AU/mL (6.4 times the upper normal limit) had 76% sensitivity, 100% specificity, with a 100% PPV, and 17% NPV for diagnosing CD (95% CI, 0.75–1). This cut-off may be used in combination with clinical judgment to diagnose CD.

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)