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OBJECTIVE: Aim: To estimate the differences between patients with celiac disease based on symptoms, diagnosis, treatment, and follow-up. PATIENTS AND METHODS: Materials and Methods: A retrospective cross-sectional study carried out between July 1, 2022 and April 2023, enrolling 200 patients from different provinces of central and south Iraq with Celia disease, whose diagnosis depended on a specialized physician according to WHO guidelines with long-term follow-up. Participants were following up for three to six months in private clinics. Survey was written in English, and the questionnaire form contains 13 fields divided into three sections. Diagnosis of Celia before and after treatment parameters: Tissue Transglutaminase Antibody, IgG, Serum (tTg-Ig G), and tTg-IgA levels the fourth part included a glutin-free diet and symptomatic treatment. RESULTS: Results: Females and ages below 20 were most affected. 176(88%) patients had detectable tTG levels; after 3 months, 72(36.0%) patients had an increase in their body weight but less than 5 kg, while 14(7.0%) of the patients showed an increase of more than 5 kg. But after 6 months, 73(36.5%) patients had an increase in their body weight less than 5 kg, while 45(22.5%) of patients showed an increase of more than 5 kg. CONCLUSION: Conclusions: Celiac patient profile in central Iraq is not different from that in other parts of the world, with typical patient being female and under 30 years of age. The study highlighted to a certain degree that a gluten-free diet can have a modest and promising positive impact on BMI in some patients.
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Enfermedad Celíaca , Humanos , Enfermedad Celíaca/dietoterapia , Enfermedad Celíaca/terapia , Enfermedad Celíaca/epidemiología , Enfermedad Celíaca/diagnóstico , Irak/epidemiología , Femenino , Masculino , Estudios Transversales , Estudios Retrospectivos , Adulto , Adulto Joven , Adolescente , Dieta Sin Gluten , Persona de Mediana Edad , Transglutaminasas/inmunología , Niño , Inmunoglobulina G/sangreRESUMEN
Glioblastoma (GBM) is one of the most aggressive cancers, characterized by a decrease in antioxidant levels. Evidence has demonstrated that ferulic acid (FA), a natural antioxidant particularly abundant in vegetables and fruits, could be a promising candidate for GBM treatment. Since FA shows a high instability that compromises its therapeutic application, it has been encapsulated into Nanostructured Lipid Carriers (NLCs) to improve its bioavailability in the brain. It has been demonstrated that tissue transglutaminase (TG2) is a multi-functional protein implicated in many physiological and pathological processes, including cancer. TG2 is also involved in GBM correlated with metastasis formation and drug resistance. Therefore, the evaluation of TG2 expression levels and its cellular localization are important to assess the anti-cancer effect of FA against GBM cancer. Our results have demonstrated that treatment with free FA and FA-NLCs in the U87-MG cancer cell line differently modified TG2 localization and expression levels. In the cells treated with free FA, TG2 appeared expressed both in the cytosol and in the nucleus, while the treatment with FA-NLCs showed that the protein is exclusively localized in the cytosol, exerting its pro-apoptotic effect. Therefore, our data suggest that FA loaded in NLCs could represent a promising natural agent for supplementing the current anti-cancer drugs used for the treatment of GBM.
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Ácidos Cumáricos , Proteínas de Unión al GTP , Glioblastoma , Nanopartículas , Proteína Glutamina Gamma Glutamiltransferasa 2 , Transglutaminasas , Ácidos Cumáricos/farmacología , Humanos , Transglutaminasas/metabolismo , Transglutaminasas/genética , Glioblastoma/metabolismo , Glioblastoma/tratamiento farmacológico , Glioblastoma/patología , Proteína Glutamina Gamma Glutamiltransferasa 2/metabolismo , Línea Celular Tumoral , Proteínas de Unión al GTP/metabolismo , Proteínas de Unión al GTP/genética , Nanopartículas/química , Portadores de Fármacos/química , Apoptosis/efectos de los fármacos , Antineoplásicos/farmacología , Neoplasias Encefálicas/tratamiento farmacológico , Neoplasias Encefálicas/metabolismo , Neoplasias Encefálicas/patología , Regulación Neoplásica de la Expresión Génica/efectos de los fármacosRESUMEN
A new chemiluminescence immunoassay method (CLIA) for detecting IgA anti-transglutaminase (atTG IgA) in celiac disease (CD) has prompted inquiries into its diagnostic performance. We conducted a systematic review and meta-analysis comparing CLIA with traditional enzyme-linked immunosorbent assay (ELISA) and fluorescence enzyme immunoassay (FEIA). We searched PubMed, Medline, and Embase databases up to March 2024. The diagnostic references were intestinal biopsy and ESPGHAN guidelines. We calculated the sensitivity and specificity of atTG IgA assessed by CLIA and the odds ratio (OR) between the assays. Eleven articles were eligible for the systematic review and seven for the meta-analysis. Sensitivity and specificity of atTG IgA CLIA-assay were 0.98 (95% CI, 0.95-0.99) and 0.97 (95% CI, 0.94-0.99), respectively. The sensitivity of atTG IgA antibody detection did not significantly vary across the three assay modalities examined (CLIA vs. ELISA OR: 1.08 (95% CI, 0.56-2.11; p = 0.8); CLIA vs. FEIA OR: 6.97 (95% CI, 0.60-81.03; p = 0.1). The specificity of atTG IgA assessed by FEIA was higher than for CLIA (OR 0.17 (95% CI, 0.05-0.62); p < 0.007). According to the systematic review, normalization of atTG IgA levels in CD patients following a gluten-free diet was delayed when using CLIA compared to ELISA and FEIA methods. Conflicting findings were reported on the antibody threshold to use in order to avoid biopsy confirmation.
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Enfermedad Celíaca , Ensayo de Inmunoadsorción Enzimática , Inmunoglobulina A , Mediciones Luminiscentes , Transglutaminasas , Humanos , Enfermedad Celíaca/diagnóstico , Enfermedad Celíaca/inmunología , Transglutaminasas/inmunología , Inmunoglobulina A/sangre , Mediciones Luminiscentes/métodos , Ensayo de Inmunoadsorción Enzimática/métodos , Sensibilidad y Especificidad , Autoanticuerpos/sangre , LuminiscenciaRESUMEN
BACKGROUND: Iron deficiency (ID) is one of the most common manifestations of Celiac disease (CD). We aimed to determine whether ID at CD diagnosis affects tissue transglutaminase antibody (TTG) normalization rate among pediatric CD patients adhering to a gluten-free diet (GFD). METHODS: We conducted a retrospective, observational cohort study that enrolled CD subjects aged 2-18y, diagnosed between Jan 2016 and Dec 2020. Demographic and laboratory data were collected at diagnosis and one year after adherence to GFD. ID was determined according to hemoglobin and ferritin levels. We compared CD subjects with and without ID at CD diagnosis in relation to TTG normalization at one year. RESULTS: Our cohort included 118 pediatric CD subjects. At diagnosis, 61 (51.7%) of CD subjects had ID, of whom 27 (44.3%) were female, compared to 46 (80.7%) females in the non-ID group (p<0.001). Median age at CD diagnosis was 5.7y (IQR 4-8.4, range 2-14) and 7.2y (IQR 4.7-10.8, range 0.9-16), and among those with and without ID, respectively (p=0.1). After one year of adherence to GFD, TTG normalization was achieved in 38 (65.5%) and 28 (53.8%) of those with and without ID at CD diagnosis, respectively (p=0.21). However, TTG normalization was achieved in 38 (79.2%) of males compared to 42 (49.4%) of females (p=0.001). CONCLUSIONS: ID at CD diagnosis was not associated with lower rates of TTG normalization at one year among pediatric patients adhering to GFD. However, TTG normalization at one year was significantly more frequent among male subjects compared to females.
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Microbial transglutaminase (mTG) is a frequently consumed processed food additive, and use of its cross-linked complexes is expanding rapidly. It was designated as a processing aid and was granted the generally recognized as safe (GRAS) classification decades ago, thus avoiding thorough assessment according to current criteria of toxicity and public health safety. In contrast to the manufacturer's declarations and claims, mTG and/or its transamidated complexes are proinflammatory, immunogenic, allergenic, pathogenic, and potentially toxic, hence raising concerns for public health. Being a member of the transglutaminase family and functionally imitating the tissue transglutaminase, mTG was recently identified as a potential inducer of celiac disease. Microbial transglutaminase and its docked complexes have numerous detrimental effects. Those harmful aspects are denied by the manufacturers, who claim the enzyme is deactivated when heated or by gastric acidity, and that its covalently linked isopeptide bonds are safe. The present narrative review describes the potential side effects of mTG, highlighting its thermostability and activity over a broad pH range, thus, challenging the manufacturers' and distributers' safety claims. The national food regulatory authorities and the scientific community are urged to reevaluate mTG's GRAS status, prioritizing public health protection against the possible risks associated with this enzyme and its health-damaging consequences.
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Potential celiac disease (PCD) is a clinical condition characterised by the presence of a positive CD-specific serology and a normal intestinal architecture. Asymptomatic PCD patients are generally advised to continue on a gluten-containing diet (GCD), but long-term risks of this approach have never been explored. In the present study, we aimed to investigate nutritional and autoimmune complications possibly developing overtime in a cohort of asymptomatic PCD children on a GCD. We compared children's parameters of growth, nutritional status, and autoimmunity between the time of diagnosis and on the occasion of their last medical check, after a long-term gluten-containing diet. Altogether, we collected data from 171 PCD children with a mean follow-up time of 3 years (range 0.35-15.3 years). During follow-up, although patients did not reduce their amount of daily gluten intake, their anti-tissue transglutaminase (anti-TG2) antibodies spontaneously and significantly decreased. Most parameters analysed had not changed during follow-up (height centile, ferritin, albumin, cholesterol, calcium, alkaline phosphatase, parathormone, and vitamin D) or even improved significantly (weight and BMI centile, haemoglobin, blood iron, HDL, glycaemia, and HbA1C, p < 0.05), always remaining within the limit of normality. Equally, autoantibodies for other concomitant autoimmune disorders did not increase overtime. Similar results were obtained excluding from analysis patients who had stopped producing anti-TG2 and those with a follow-up time < 3 years. Our pilot study has provided reassuring results regarding the maintenance of a gluten-containing diet in asymptomatic PCD children, even when long-term follow-up was considered.
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Autoanticuerpos , Enfermedad Celíaca , Dieta Sin Gluten , Estado Nutricional , Humanos , Enfermedad Celíaca/dietoterapia , Enfermedad Celíaca/inmunología , Niño , Masculino , Femenino , Preescolar , Adolescente , Autoanticuerpos/sangre , Proteína Glutamina Gamma Glutamiltransferasa 2 , Proteínas de Unión al GTP/inmunología , Transglutaminasas/inmunología , Glútenes/efectos adversos , Glútenes/inmunología , Estado de Salud , Lactante , Estudios de Seguimiento , AutoinmunidadRESUMEN
OBJECTIVES: European Society for Paediatric Gastroenterology, Hepatology and Nutrition (ESPGHAN) guidelines enable the diagnosis of celiac disease (CD) without biopsies in patients with immunoglobulin A (IgA)-antibodies against tissue transglutaminase (TGA-IgA) ≥ 10× the upper limit of normal (ULN) and positivity of endomysial antibodies in a second blood sample. Limited data exist comparing the biopsy versus the nonbiopsy diagnostic approach regarding long-term outcomes in CD patients. Our study aimed to investigate the influence of the diagnostic approach on adherence to gluten-free diet (GFD), serological remission (defined as normalization of TGA-IgA during follow-up (FU)) and clinical remission in CD patients with TGA-IgA ≥ 10× ULN. METHODS: Retrospective multicenter study. Patients with CD and TGA-IgA ≥ 10× ULN at diagnosis were included in the study. Patients with confirmed diagnosis by biopsy were compared to patients diagnosed by nonbiopsy approach using univariate analysis, Kaplan-Meier survival curve, and logistic regression models. RESULTS: A total of 282 CD patients (192 [68.1%] in the biopsy group; 90 [31.9%] in the nonbiopsy group) were analyzed. The median time to normalization of TGA-IgA was 16.5 months [interquartile range, IQR: 13, 28] in the biopsy and 15 months [IQR: 12, 26] in the nonbiopsy group; p = 0.14). Rates of normalized TGA-IgA at first to third-year FU were comparable between both groups. Adherence to GFD did not seem to be influenced by the diagnostic approach. CONCLUSIONS: The nonbiopsy approach is not inferior to the biopsy approach in terms of adherence to GFD and serological remission in patients with CD.
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Enfermedad Celíaca , Dieta Sin Gluten , Inmunoglobulina A , Transglutaminasas , Humanos , Enfermedad Celíaca/diagnóstico , Enfermedad Celíaca/dietoterapia , Enfermedad Celíaca/sangre , Enfermedad Celíaca/inmunología , Estudios Retrospectivos , Masculino , Niño , Femenino , Biopsia , Transglutaminasas/inmunología , Preescolar , Adolescente , Inmunoglobulina A/sangre , Autoanticuerpos/sangre , Proteína Glutamina Gamma Glutamiltransferasa 2 , Proteínas de Unión al GTP/inmunología , Resultado del Tratamiento , Estudios de Seguimiento , Lactante , Cooperación del PacienteRESUMEN
AIM: To compare the adherence to gluten-free diet between children with serology-based and biopsy-proven coeliac disease. METHODS: Medical records were retrospectively reviewed in 257 Swedish children diagnosed with coeliac disease between 2012 and 2019 at a tertiary hospital. Adherence to a gluten-free diet was systematically assessed by trained dietitians at follow-up. Mixed models were used to analyse the dietary adherence by mode of diagnosis (serology-based vs. biopsy-proven). RESULTS: After mean 6.3 (SD 2.4) years, there was neither a difference in the dietary adherence over time depending on the mode of diagnosis (OR 0.64 [95% confidence interval (CI) 0.26, 1.60], p = 0.342), nor if coeliac disease was detected in screening studies (OR 0.74 [95% CI 0.25, 2.17], p = 0.584) or in risk-groups (OR 1.01 [95% CI 0.26, 3.91], p = 0.991) compared to clinically detected diagnosis. Non-adherence to a gluten-free diet increased with age (OR 1.19 [95% CI 1.06, 1.33], p = 0.003). There was no difference in the proportion of patients improving their dietary adherence from non-adherent to adherent over time (p = 0.322). CONCLUSION: Mode of diagnosis did not influence the dietary adherence in Swedish children with coeliac disease, although adherence to a gluten-free diet was inversely associated with increasing age.
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Enfermedad Celíaca , Dieta Sin Gluten , Cooperación del Paciente , Humanos , Enfermedad Celíaca/dietoterapia , Enfermedad Celíaca/diagnóstico , Masculino , Femenino , Estudios Retrospectivos , Niño , Cooperación del Paciente/estadística & datos numéricos , Preescolar , Suecia , AdolescenteRESUMEN
Gluten ataxia and other central nervous system disorders could be linked to gluten enteropathy and related autoantibodies. In this narrative review, we focus on the various neuro-logical manifestations in patients with gluten sensitivity/celiac disease, immunological and autoimmune mechanisms of ataxia in connection to gluten sensitivity and the autoantibodies that could be used as a biomarker for diagnosing and following. We focused on the anti-gliadin antibodies, antibodies to different isoforms of tissue transglutaminase (TG) (anti-TG2, 3, and 6 antibodies), anti-glycine receptor antibodies, anti-glutamine acid decarboxylase antibodies, anti-deamidated gliadin peptides antibodies, etc. Most studies found a higher prevalence of these antibodies in patients with gluten sensitivity and neurological dysfunction, presented as different neurological disorders. We also discuss the role of a gluten-free diet on the clinical improvement of patients and also on imaging of these disorders.
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BACKGROUND: Laboratory testing for celiac disease in pediatric patients integrates serology, genetic susceptibility and duodenal biopsy examination. The 2023 American College of Gastroenterology guidelines recommend a biopsy-free approach in pediatric patients utilizing tissue transglutaminase antibody titers >10 times upper limit of normal and subsequent endomysial antibody seropositivity as sufficient for diagnosis. The objective of this study is to assess the diagnostic accuracy of biopsy-free approach at our pediatric hospital. METHODS: We conducted a retrospective study involving pediatric patients who underwent biopsy for diagnostic confirmation of celiac disease between May 2019 and May 2023. For these patients, the tissue transglutaminase and endomysial antibody test results were retrieved and performance of biopsy-free approach was assessed using the duodenal histology as the gold standard for celiac disease diagnosis. RESULTS: Tissue transglutaminase antibody titers >10 times upper limit of normal alone demonstrated a positive predictive value of 99% for identifying celiac disease in children. Although endomysial antibody testing is underutilized at our center, its inclusion further improved the predictability to 100 %. CONCLUSION: Positive predictive value of tissue transglutaminase antibody titers >10 times upper limit of normal is sufficiently high for celiac disease diagnosis in children and may allow for deferral of duodenal biopsy at diagnosis.
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Enfermedad Celíaca , Proteína Glutamina Gamma Glutamiltransferasa 2 , Niño , Humanos , Enfermedad Celíaca/diagnóstico , Enfermedad Celíaca/patología , Estudios Retrospectivos , Transglutaminasas , Proteínas de Unión al GTP , Inmunoglobulina A , Biopsia , AutoanticuerposRESUMEN
OBJECTIVE: To evaluate the relationship between genetic haplotypes associated with celiac disease (Human Leucocyte Antigen [HLA] DQ2 and DQ8) with the diagnosis, clinical presentation, and location of endometriosis in Brazilian women. METHOD: A retrospective cross-sectional study, was conducted in a Tertiary hospital. PATIENTS: Women aged 18-50 years who underwent HLA-DQ2 and HLA-DQ8 haplotype analysis. INTERVENTION: The patients were divided into endometriosis and control groups and evaluated for symptoms; endometriosis location, American Society for Reproductive Medicine (ASRM) stage, and the presence of anti-tissue transglutaminase IgA (anti-TgA), HLA-DQ2, and HLA-DQ8 markers. RESULTS: A total of 434 consecutive patients with (n = 315) and without (n = 119) endometriosis were included. Pain and infertility were more frequent in the endometriosis group than in the control group. The presence of HLA-DQ2, HLA-DQ8, and anti-TgA was similar between both groups. The presence of HLA-DQ2 and HLA-DQ8 markers did not differ based on age, pain symptoms, ASRM stage, or endometriosis location. CONCLUSION: Although there are similarities in inflammatory markers and pathophysiology between celiac disease and endometriosis, this study found no significant associations in the presence of HLA-DQ2 or HLA-DQ8 haplotypes and endometriosis.
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Enfermedad Celíaca , Endometriosis , Antígenos HLA-DQ , Humanos , Femenino , Endometriosis/genética , Estudios de Casos y Controles , Estudios Retrospectivos , Haplotipos , Enfermedad Celíaca/genética , Estudios Transversales , DolorRESUMEN
OBJECTIVES: Autoantibodies against tissue transglutaminase (tTG) are serological markers of celiac disease. The aim was to study the applicability of human leukocyte antigen (HLA)-genotyping and tTG autoantibodies in the screening of celiac disease in a longitudinal birth cohort followed to age 15 years. METHODS: Included were 13,860 HLA-DQ-genotyped children at birth and previously invited to a screening at age 3 and 9 years, respectively. HLA-DQB1*02 and/or DQB1*03:02 (HLA-risk) children were compared with non-HLA-DQB1*02 and non-DQB1*03:02 (HLA-nonrisk) children. The present study reinvited 12,948/13,860 (93.4%) children at age 15 years of whom 1056/2374 (44.5%) participated in screening at both age 3 and 9 years. Both immunoglobulin A (IgA) and G (IgG) autoantibodies against tTG were analyzed separately in radiobinding assays. Persistently tTG autoantibody-positive children were examined with intestinal biopsy to confirm the diagnosis of celiac disease. RESULTS: At age 3 years, celiac disease was diagnosed in 56/1635 (3.4%) HLA-risk children compared with 0/1824 HLA-nonrisk children (p < 0.001). By age 9 years, celiac disease was diagnosed in 72/1910 (3.8%) HLA-risk children compared with 0/2167 HLA-nonrisk children (p < 0.001). Screening at age 15 years detected 14/1071 (1.3%) HLA-risk children positive for IgA-tTG and/or IgG-tTG of whom 12/1071 (1.1%) remained persistently positive. Among those, 10/1071 (0.9%, 95% confidence interval: 0.4%-1.7%) HLA-risk children were diagnosed with celiac disease compared with 0/1303 HLA-nonrisk children (p < 0.001) and 5/491 (1.0%) were negative in screenings at both 3 and 9 years of age. CONCLUSIONS: Screening for celiac disease needs to be performed at multiple timepoints to detect all cases but can be restricted to children at HLA-risk.
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Autoanticuerpos , Enfermedad Celíaca , Proteínas de Unión al GTP , Inmunoglobulina A , Transglutaminasas , Humanos , Enfermedad Celíaca/diagnóstico , Enfermedad Celíaca/inmunología , Enfermedad Celíaca/genética , Niño , Preescolar , Transglutaminasas/inmunología , Estudios Longitudinales , Autoanticuerpos/sangre , Adolescente , Femenino , Masculino , Inmunoglobulina A/sangre , Proteínas de Unión al GTP/inmunología , Inmunoglobulina G/sangre , Proteína Glutamina Gamma Glutamiltransferasa 2 , Antígenos HLA-DQ/genética , Tamizaje Masivo/métodos , Genotipo , Cadenas beta de HLA-DQ/genética , Factores de Riesgo , Predisposición Genética a la EnfermedadRESUMEN
The accumulating data regarding a non-biopsy diagnosis of celiac disease has led to its adoption in certain scenarios, although debate on whether and when to use non-biopsy criteria in clinical practice is ongoing. Despite the growing popularity and evidence basis for a biopsy-free approach to diagnosis in the context of highly elevated serologies, there will continue to be a role for a biopsy in some groups. This review summarizes the current evidence supporting a non-biopsy approach and arguments supporting continued reliance on biopsy, and focuses on opportunities to improve both approaches.
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Enfermedad Celíaca , Enfermedad Celíaca/diagnóstico , Enfermedad Celíaca/patología , Humanos , Biopsia , Valor Predictivo de las PruebasRESUMEN
Celiac disease (CeD) is a chronic immune-mediated enteropathy, which occurs in genetically predisposed individuals by the ingestion of gluten proteins present in wheat, barley and rye. The global pooled prevalence of CeD is 0.7% and it has been reported from nations all around the globe and can affect individuals of any age. It has a wide clinical spectrum ranging from being asymptomatic to being symptomatic with severe manifestations. Though initial descriptions of CeD focused on the classical presentation with gastrointestinal manifestations, in recent years it has been found that more patients have non-classical manifestations such as anemia, osteoporosis, increased transaminases, failure to thrive or short stature. The definitive diagnosis of CeD is based on a combination of clinical history, serologic testing with/without examination of duodenal biopsies. The preferred initial serologic test regardless of age for the detection of CeD is the tissue transglutaminase (IgA anti-tTG). Children with a high tTG-IgA (≥10 ULN) AND a positive anti-endomysial IgA antibody (EMA) can be diagnosed to have CeD without the need for duodenal biopsies. The rest should undergo biopsies with at least 4 biopsies from the distal duodenum and at least 1 from the bulb. A correctly orientated biopsy showing increased intraepithelial cells and a villous to crypt ratio of <2 is suggestive of CeD. The management of CeD is a lifelong complete dietary avoidance of gluten. IgA-TGA acts as a surrogate marker for healing of the small-bowel mucosa and should be performed every 6 mo until normalization and then every 12-24 mo thereafter.
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Enfermedad Celíaca , Niño , Humanos , Enfermedad Celíaca/diagnóstico , Transglutaminasas , Duodeno/patología , Biopsia , Inmunoglobulina A , Glútenes , AutoanticuerposRESUMEN
Clock gene disruption has been reported in inflammatory and autoimmune diseases. Specifically, it has been shown that clock gene expression is down-regulated in intestinal tissue and peripheral blood mononuclear cells of patients with inflammatory bowel disease (IBD). We aimed to determine the systemic expression of the circadian clock genes in newly diagnosed untreated, young patients with celiac disease (CeD). We prospectively enrolled patients younger than 20 years old who underwent diagnostic endoscopic procedures either for CeD diagnosis or due to other gastrointestinal complaints, at the pediatric and adult gastroenterology units, the Tel Aviv Sourasky Medical Center from 8/2016-8/2022. Demographic data, anthropometric parameters, and endoscopic macroscopic and microscopic findings were obtained. Blood samples were obtained to determine tissue transglutaminase (tTG) and core clock gene (CLOCK, BMAL1, PER1, PER2, CRY1, CRY2) expression in white blood cells (WBC). Thirty individuals were analyzed (18 with newly diagnosed CeD and 12 controls). Expression of the clock genes CLOCK, BMAL1, CRY2, PER1 and PER2 was significantly reduced in CeD patients compared to controls, while CRY1 did not differ between the groups. In conclusion, newly diagnosed, untreated, young patients with CeD have reduced clock gene expression in WBC compared to controls. These results suggest that, in CeD, the inflammatory response is associated with systemic disruption of clock gene expression, as is manifested in other inflammatory and autoimmune diseases. CLINICALTRIALS.GOV IDENTIFIER: NCT03662646.
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Enfermedades Autoinmunes , Enfermedad Celíaca , Relojes Circadianos , Adulto , Humanos , Niño , Adulto Joven , Relojes Circadianos/genética , Ritmo Circadiano/genética , Leucocitos Mononucleares , Factores de Transcripción ARNTL/genética , Enfermedad Celíaca/genéticaRESUMEN
OBJECTIVES: Tissue transglutaminase (tTG) IgA antibodies are a hallmark for celiac disease (CD). In CD patients on gluten free diet (GFD) these antibodies are transient. Few studies are available comparing the tTG-IgA assay characteristics for monitoring response to GFD. Since discrepant results were reported in patients on GFD after switching tTG-IgA assays, we conducted a retrospective observational study to monitor GFD response using three different tTG-IgA assays. METHODS: Diagnostic samples from 44 adults and 17 children with CD were included. Of most patients two follow-up samples after introduction of GFD were available. In all samples tTG-IgA were assessed using one fluorochrome-enzyme immuno-assay (FEIA) and two chemiluminescence immuno-assays (CLIA) and intestinal fatty acid binding protein (i-FABP) as surrogate marker for intestinal epithelial damage was measured. RESULTS: Using CLIA assays, normalization of antibody levels was delayed compared to FEIA (p<0.001). Of all samples taken after at least 6â¯months on GFD with elevated i-FABP indicating intestinal epithelial damage, 40â¯% had positive tTG-IgA according to the FEIA, 85 and 90â¯% according to the two CLIA. CONCLUSIONS: Normalization of tTG-IgA in patients on GFD depends on the assay used. Both CLIA appear to be more sensitive in detecting suboptimal treatment response in CD-indicated by elevated i-FABP - when applying the manufacturer's recommended cut-off for the diagnosis of CD.
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Enfermedad Celíaca , Niño , Adulto , Humanos , Enfermedad Celíaca/diagnóstico , Dieta Sin Gluten , Proteína Glutamina Gamma Glutamiltransferasa 2 , Transglutaminasas , Autoanticuerpos , Inmunoglobulina ARESUMEN
BACKGROUND: The prevalence of coeliac disease doubled in Finland from 1980 to 2000. AIMS: To investigate whether this increase is continuing and if there are specific patient-related factors predicting the development of coeliac disease at a population level. METHODS: We elicited comprehensive health data in the nationwide Health 2000 and Health 2011 surveys. Serum samples were taken for the measurement of tissue transglutaminase antibodies (TGA); subjects who were seropositive were tested for endomysial antibodies (EmA). Coeliac disease was defined either as a reported diagnosis or as positive TGA and EmA. The surveys comprised, respectively, 6379 and 4056 individuals, forming representative samples for 2,946,057 and 2,079,438 Finnish adults. Altogether 3254 individuals participating in both surveys comprised a prospective follow-up cohort. RESULTS: Prevalence of coeliac disease was 2.12% in 2000 and 2.40% in 2011 (p = 0.156). In the prospective cohort, 16 out of the 3254 (0.49%) subjects developed coeliac disease during follow-up from 2000 to 2011, with an annual incidence rate of 45 per 100,000 persons. Positive TGA without EmA (OR: 133, 95% CI: 30.3-584), TGA values in the upper normal range (51.1, 16.0-163), and after adjusting for TGA, previous autoimmune co-morbidity (8.39, 4.98-35.9) in 2000 increased the likelihood of subsequent coeliac disease. CONCLUSIONS: The nationwide prevalence of coeliac disease kept on rising from 2.12% in 2000 to 2.40% in 2011 in Finland. Positive TGA without EmA, TGA titres in the upper normal range and a pre-existing autoimmune disease predisposed to coeliac disease during the 10-year follow-up.
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Enfermedad Celíaca , Adulto , Humanos , Enfermedad Celíaca/diagnóstico , Enfermedad Celíaca/epidemiología , Estudios de Seguimiento , Transglutaminasas , Estudios Prospectivos , Prevalencia , Autoanticuerpos , Inmunoglobulina ARESUMEN
BACKGROUND AND AIM: While European Society of Pediatric Gastroenterology Hepatology and Nutrition advocates a no-biopsy pathway for the diagnosis of celiac disease (CeD) in children if IgA anti-tissue transglutaminase antibody (anti-tTG ab) titer is ≥10-fold upper limit of normal (ULN) and have a positive IgA anti-endomysial antibody (EMA); the data for anti-tTG Ab titer-based diagnosis of CeD in adults is still emerging. We planned to validate if IgA anti-tTG Ab titer ≥10-fold predicts villous abnormalities of modified Marsh grade ≥2 in Asian adult patients with CeD. METHODS: We recruited 937 adult patients with positive anti-tTG Ab from two databases, including AIIMS Celiac Clinic and Indian National Biorepository. The diagnosis of definite CeD was made on the basis of a positive anti-tTG Ab and the presence of villous abnormalities of modified Marsh grade ≥2. RESULTS: Of 937 adult patients with positive anti-tTG Ab, 889 (91.2%) showed villous abnormalities of modified Marsh grade ≥2. Only 47.6% of 889 adults with CeD had anti- tTG Ab titers of ≥10-fold. The positive predictive value (PPV) and specificity of anti tTG Ab titer ≥10-fold for predicting modified Marsh grade ≥2 were 99.8% and 98%, respectively. At anti-tTG Ab titer ≥11-fold, specificity and PPV were 100% for predicting villous abnormalities of modified Marsh grade ≥2. CONCLUSIONS: Approximately 50% of adults with CeD may benefit from the no biopsy pathway, reducing the health burden and risks of gastroscopy/anesthesia.
Asunto(s)
Enfermedad Celíaca , Adulto , Humanos , Autoanticuerpos , Enfermedad Celíaca/patología , Proteínas de Unión al GTP , Inmunoglobulina A , Proteína Glutamina Gamma Glutamiltransferasa 2 , Estudios Retrospectivos , Sensibilidad y Especificidad , TransglutaminasasRESUMEN
Abstract Objective To evaluate the relationship between genetic haplotypes associated with celiac disease (Human Leucocyte Antigen [HLA] DQ2 and DQ8) with the diagnosis, clinical presentation, and location of endometriosis in Brazilian women. Method A retrospective cross-sectional study, was conducted in a Tertiary hospital. Patients Women aged 18-50 years who underwent HLA-DQ2 and HLA-DQ8 haplotype analysis. Intervention The patients were divided into endometriosis and control groups and evaluated for symptoms; endometriosis location, American Society for Reproductive Medicine (ASRM) stage, and the presence of anti-tissue transglutaminase IgA (anti-TgA), HLA-DQ2, and HLA-DQ8 markers. Results A total of 434 consecutive patients with (n = 315) and without (n = 119) endometriosis were included. Pain and infertility were more frequent in the endometriosis group than in the control group. The presence of HLA-DQ2, HLA-DQ8, and anti-TgA was similar between both groups. The presence of HLA-DQ2 and HLA-DQ8 markers did not differ based on age, pain symptoms, ASRM stage, or endometriosis location. Conclusion Although there are similarities in inflammatory markers and pathophysiology between celiac disease and endometriosis, this study found no significant associations in the presence of HLA-DQ2 or HLA-DQ8 haplotypes and endometriosis.