Julio C Bai
Universidad del Salvador (USAL), Gastroenterología, Faculty Member
Coeliac disease is a systemic disorder characterized by immune-mediated enteropathy, which is caused by gluten ingestion in genetically susceptible individuals. The clinical presentation of coeliac disease is highly variable and ranges... more
Coeliac disease is a systemic disorder characterized by immune-mediated enteropathy, which is caused by gluten ingestion in genetically susceptible individuals. The clinical presentation of coeliac disease is highly variable and ranges from malabsorption through solely extra-intestinal manifestations to asymptomatic. As a result, the majority of patients with coeliac disease remain undiagnosed, misdiagnosed or experience a substantial delay in diagnosis. Coeliac disease is diagnosed by a combination of serological findings of disease-related antibodies and histological evidence of villous abnormalities in duodenal biopsy samples. However, variability in histological grading and in the diagnostic performance of some commercially available serological tests remains unacceptably high and confirmatory assays are not readily available in many parts of the world. Currently, the only effective treatment for coeliac disease is a lifelong, strict, gluten-free diet. However, many barriers impede patients’ adherence to this diet, including lack of widespread availability, high cost, cross-contamination and its overall restrictive nature. Routine follow-up is necessary to ensure adherence to a gluten-free diet but considerable variation is evident in follow-up protocols and the optimal disease management strategy is not clear. However, these challenges in the diagnosis and management of coeliac disease suggest opportunities for future research. Despite advances in testing for coeliac disease over the past two decades, awareness of this disease remains suboptimal worldwide. Here, Makharia and colleagues summarize the current knowledge of epidemiology, risk factors, diagnosis and follow-up of coeliac disease and highlight opportunities for future research. Coeliac disease is a global disease with a worldwide prevalence of around 1%. Most patients with coeliac disease are undiagnosed, misdiagnosed and/or experience a substantial delay in diagnosis, which suggests an inadequate awareness of the spectrum of its clinical manifestations. Despite improvements in the diagnosis of coeliac disease, persistent challenges include high inter-assay and intra-assay variation in serological test performance and high inter-observer variability in the grading of villous abnormalities. The optimal follow-up strategy for coeliac disease is unclear and studies are needed to define the timing and role of serological testing, gluten immunogenic peptide measurement and repeat biopsy. Increased access to dietitians, improved tools to assess adherence to a gluten-free diet, increased availability of gluten-free foods and reduced gluten contamination of gluten-free food products are needed. As maintaining strict adherence to a gluten-free diet is restrictive and challenging, the development of adjunct or alternative non-dietary therapies for coeliac disease is crucial. Coeliac disease is a global disease with a worldwide prevalence of around 1%. Most patients with coeliac disease are undiagnosed, misdiagnosed and/or experience a substantial delay in diagnosis, which suggests an inadequate awareness of the spectrum of its clinical manifestations. Despite improvements in the diagnosis of coeliac disease, persistent challenges include high inter-assay and intra-assay variation in serological test performance and high inter-observer variability in the grading of villous abnormalities. The optimal follow-up strategy for coeliac disease is unclear and studies are needed to define the timing and role of serological testing, gluten immunogenic peptide measurement and repeat biopsy. Increased access to dietitians, improved tools to assess adherence to a gluten-free diet, increased availability of gluten-free foods and reduced gluten contamination of gluten-free food products are needed. As maintaining strict adherence to a gluten-free diet is restrictive and challenging, the development of adjunct or alternative non-dietary therapies for coeliac disease is crucial.
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Serology has significantly revolutionized the knowledge of celiac disease (CD), leading to the identification of unsuspected patients in at-risk CD groups, thereby increasing the number of CD diagnoses compared to the pre-screening era.... more
Serology has significantly revolutionized the knowledge of celiac disease (CD), leading to the identification of unsuspected patients in at-risk CD groups, thereby increasing the number of CD diagnoses compared to the pre-screening era. Several markers for CD with a progressive diagnostic accuracy have been identified over the years, but only three of them, i.e. anti-tissue transglutaminase (anti-tTG), anti-endomysial (EmA) and anti-deamidated gliadin antibodies (DGP) are currently assessed in the daily clinical practice. A thorough review of the literature identified 44 original studies published between 1998 to 2022 for a total of 5098 pediatric and adult CD patients (without selective IgA deficiency) and 11930 disease controls. The results highlighted that anti-tTG IgA exhibited a higher sensitivity for CD (93.4%) than EmA IgA (92.8%), DGP IgG (81.8%) and DGP IgA (83.8%). The specificity of EmA IgA (99%) resulted to be higher than those of anti-tTG IgA (95.8%), DGP IgG (96.4%) and DGP IgA (92.1%). In patients with selective IgA deficiency, a condition closely related to CD, serological screening should include one of the three antibodies of IgG class, since anti-tTG, DGP and EmA have a very similar diagnostic accuracy in this clinical setting. According to age, there are two main diagnostic strategies for CD detection. In children, the revised ESPGHAN 2020 guidelines established that CD could be diagnosed in both symptomatic and asymptomatic children by high anti-tTG IgA titers (>10 times the cut-off) and EmA positivity with no need to obtain duodenal biopsy and HLA typing. In adult patients, although high tTG IgA titers (confirmed by EmA IgA positivity) correlate with villous atrophy, an intestinal biopsy is still considered mandatory for confirming CD diagnosis. Currently, a case finding approach in at-risk groups is preferred to mass screening for CD detection.
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In previous study in our laboratory, we had shown the effect of radiation on morphometry of small bowel of rats after 7 days of a single external doses of 1,000 rads with liver protection. Our aim was to determine the effect of the same... more
In previous study in our laboratory, we had shown the effect of radiation on morphometry of small bowel of rats after 7 days of a single external doses of 1,000 rads with liver protection. Our aim was to determine the effect of the same procedure of gamma radiation in rats on the morphometry and D-Xylose absorption 7, 14 and 21 days after injury and compared with a control group matched by weight. The D-Xylose absorption was measured by plasmatic D-Xylose, 60' after an intragastric doses of the pentose (0.5 grs/kg of body weight). Results: In the control group the mucosal thickness was 880 +/- 40 mu (X +/- SD), the vellous height was 640 +/- 37.6 mu and the xylosemia 15.91 +/- 11.39 mg%. At 7 days in the irradiated group (n: 11) the weight decreased 33.36 +/- 6.29% (Vs. control p less than .001), the mucosal thickness and the vellous height were 666 +/- 97 (p less than .001) and 466 +/- 66.9 mu (p less than .001) and the xylosemia 6.16 +/- 2.3 (p less than .05). The figures at 14 days (n: 16) showed improving and completed recovery at 21 days (n: 14). Irradiated rats were shown to be affected in weight, morphology and D-Xylose absorption, they began recovering after 7 days, and completed recovery at 21 days.
Research Interests: Chemistry, Gamma Rays, Medicine, Intestinal Mucosa, Pubmed, and 7 moreAnimals, Jejunum, Clinical Sciences, Rats, Irradiation, Body Weight, and Xylose
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Background: Refractory sprue (RS) is a rare and severe celiac-like enteropathy not responding to a strict gluten-free diet. Although prognosis is generally poor, little is known about the long-term outcome of patients. Aim: to report... more
Background: Refractory sprue (RS) is a rare and severe celiac-like enteropathy not responding to a strict gluten-free diet. Although prognosis is generally poor, little is known about the long-term outcome of patients. Aim: to report baseline characteristics and long-term outcome of a series of patients diagnosed and treated in a single institution. Materials: We report a retrospective cohort of 25 consecutive patients (15 females; mean age 46 yr; range 28-71) diagnosed with RS based on the presence of a non-responsive celiac-like enteropathy. All patients were intensively treated with a gluten-free diet, steroids, nutritional support and immunosupression. Results: Clinical and biological characteristics of patients suggest that, at least, 24 patients had clear evidences of celiac disease. HLA DQ2/DQ8 genes were present in all the 24 patients typed and autoimmune enteropathy was excluded in all. According to the genotyping, 12 patients had a polyclonal lymphocyte population (RS type I) and 13 exhibited monoclonal TCR-gamma gene rearrangements (RS type II). Sixteen patients had evidence of ulcerative jejunitis (UJ) (7 in RS type I and 9 in type II). Overall median follow-up time after diagnosis of RS was 29 mo/patient (range 7 to 204) (45 mo for type I and 24 mo for type II). Overall mortality was 48% (12 patients), 6 in each type. Eight patients with UJ (50%), 3 with lymphoma (two T-cell and one B-cell type) and 4 (44%) without ulcers died during follow-up. The causes of death were sepsis in the context of a progressive deterioration but without overt malignancies (n=5), vascular causes (n=3) and severe malnutrition (n=1). Three- and 5-yr survival rate after diagnosis of RS for the overall population was 60% and 56%. There was no differences between type I (67%, 58%) and type II RS patients (54% for both periods). Patients with UJ had lower but non-significant 3- and 5-yr survival rates (56% and 50%, respectively) compared with patients without ulcers (78% and 66%). Survivors had a favorable outcome. While 11 patients persists asymptomatic, two other cases still have mild diarrhea and one low body weight. Conclusions: We confirm that RS is a severe celiac disease-related disorder with very high mortality. Diagnosis of overt lymphoma (12%) in our long-term follow-up was not as frequent as was reported by other groups. A proportion of patients persist in good health for a long time irrespective of the nature of the IEL infiltration or the presence of UJ.
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Research Interests: Adolescent, Medicine, Humans, Internal Medicine, Celiac Disease, and 15 moreFemale, Male, Cohort, Clinical Sciences, Aged, Middle Aged, Adult, Proportional hazards model, Prognosis, Lymphocytes, Coeliac Disease, Proportional Hazards Models, Confidence Interval, Pharmacology and pharmaceutical sciences, and hazard ratio
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The World Gastroenterology Organisation aims to guide health providers in the best management of celiac disease by providing a concise document with recommendations based on the latest evidence and resulting from our global expert... more
The World Gastroenterology Organisation aims to guide health providers in the best management of celiac disease by providing a concise document with recommendations based on the latest evidence and resulting from our global expert consensus process on best current practices. In this guideline, a review team consisting of experts from 4 continents provides an updating with concepts that have been developed since the publication of the earlier guideline (2013). The guideline explores the epidemiology of the disorder from a global perspective and updates the diagnostic work-up as well as therapeutic and follow-up aspects of celiac disease. As a novelty in celiac disease, the team also provides cascades that represent a hierarchical set of diagnostic and management options to deal with the disease, ranked by available resources. The aim in presenting cascades is to highlight appropriate, context-sensitive, and resource-sensitive management options for all geographic regions, regardless of whether they are considered as “developing,” “semideveloped,” or “developed.” World Gastroenterology Organisation cascades are context-sensitive, and the context is not necessarily defined solely by resource availability. As first-line tests for symptomatic and asymptomatic patients, the experts suggest antitissue transglutaminase (antitTG) immunoglobulin A (IgA)+total IgA. However, to confirm a positive initial test, or in case of borderline tissue transglutaminase (tTG) IgA titers, it is recommended that other tests should be added, such as IgA antiendomysium, which is strongly recommended in most other guidelines. Other immunoassays regarded as good tests include the antiendomysium antibody (EMA) and immunoglobulin G-deamidated gliadin peptide (IgG-DGP) tests. A combination of IgG-DGP and IgA-tTG is particularly useful for detecting patients with celiac disease who are IgA-deficient. IgG-DGP is reported to be able to detect a few more IgA-sufficient patients who are missed on IgA-transglutaminase (IgA-tTG) tests. For some authors, performing IgA-tTG+IgG-DGP—2 tests addressing different antigens—is better than if 2 tests addressing the same autoantigen (IgA-tTG+IgA-EMA) are carried out. There was intense debate in the review team regarding the most appropriate serological strategy for diagnosing celiac disease, and we present readers with all of the various strategies here.
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The present study was designed to determine the diagnostic usefulness of videoduodenoscopic inspection alone and the addition of vital dye staining in the detection of celiac disease. We additionally sought to evaluate interobserver... more
The present study was designed to determine the diagnostic usefulness of videoduodenoscopic inspection alone and the addition of vital dye staining in the detection of celiac disease. We additionally sought to evaluate interobserver agreement for specific duodenoscopic markers of mucosal atrophy. One hundred sixty-seven consecutive subjects who underwent duodenoscopy for intestinal biopsy were included in a prospective controlled study. Endoscopic examination was performed by experienced endoscopists according to a set protocol using methylene blue (1%) dye. All procedures were recorded on videotape, but only 20 (10 with atrophy and 10 normal) were used in a blinded, independent, randomized analysis by five reviewers to evaluate interobserver agreement. Endoscopic signs indicative of mucosal atrophy were as follows: reduction in the number or loss of Kerkring's folds, "scalloped" folds, "mosaic pattern," and visualization of the underlying blood vessels. Eighty-seven patients had celiac disease (57 newly diagnosed, 30 when treated). Seven treated patients had nonatrophic mucosa. In 80 patients the final diagnosis excluded celiac disease. Videoendoscopic inspection alone correctly identified 75 of 80 patients with complete mucosal atrophy and 86 of 87 with normal mucosa. False-negative diagnoses occurred in treated celiac patients with mild atrophy. Mosaic pattern (89%) and scalloped folds (86%) were the most useful endoscopic signs. Vital dye staining, as assessed by experienced endoscopists, provided identical results to those obtained by inspection alone. Sensitivity, specificity, and positive and negative predictive values for the presence of one or more than one feature were 94%, 100%, 100%, and 96%, respectively. The agreement (kappa statistics) among observers was excellent for the mosaic pattern (kappa: 0.76 for both the videoendoscopic inspection alone and dye staining) and the scalloped folds (kappa: 0.83 and 0.76, respectively) and was fair (kappa: 0.41 and 0.59, respectively) for the reduction in the number or loss of duodenal folds. This study confirms that videoduodenoscopy is useful in the detection of intestinal atrophy. Dye staining produces a better delineation of scalloped folds and mosaic pattern in the atrophic mucosa, but did not provide additional information to the expert endoscopist. Finally, interobserver agreement was excellent for the most prevalent signs.
Research Interests: Medicine, Biopsy, Humans, Intestinal Mucosa, Celiac Disease, and 15 moreFemale, Male, Methylene Blue, Clinical Sciences, Gastrointestinal Endoscopy, Atrophy, Observer Variation, Adult, Gastrointestinal, Blood Vessel, Predictive value of tests, False Negative, Duodenum, Negative predictive value, and coloring agents
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the indication for duodenal ESD is highly controversial. EMR with a cap-fitted panendoscope (EMR-C) is known as an effective treatment for esophageal tumors in particular. Recently, we have performed EMR-C as therapy for the superficial... more
the indication for duodenal ESD is highly controversial. EMR with a cap-fitted panendoscope (EMR-C) is known as an effective treatment for esophageal tumors in particular. Recently, we have performed EMR-C as therapy for the superficial epithelial type of sporadic non-ampullary duodenal adenoma/carcinoma (SNADA) in our establishment. However, efficacy for duodenal tumors has not yet been reported. In this study, we assessed the efficacy of EMR-C for the superficial epithelial type of SNADA. Methods: We retrospectively evaluated 74 patients with SNADA who underwent endoscopic resection between May 2004 and October 2014 at our establishment. In addition, we assessed and compared the incidence rate of complications and frequency rate of en bloc resection according to the macroscopic appearance of the lesions and the methods of mucosal resection, especially of the superficial epithelial type of SNADA, between EMR-C and EMR. Results: The mean age of the patients was 63.7 12.0 years and 52 were male. Seventy-nine SNADA lesions were resected. The final pathological diagnoses, low-grade dysplasia, highgrade dysplasia, and intramucosal carcinoma were 21, 27, and 31, respectively. The mean size of the lesions was 10.5 5.8 mm. The numbers of macroscopic appearance of types Ip, Is, Is + IIa, IIa, IIa + IIc, and IIc according to the Paris endoscopic classification were 5, 9, 3, 27, 21, and 14, respectively. The numbers of lesions resected by polypectomy, EMR, EMR-C, strip biopsy, and ESD were 1, 33, 25, 9, and 11, respectively. The perforation rate with EMR and EMR-C were significantly lower than that with ESD (0% and 4.0% vs. 27.3%; p Z 0.002 and 0.041, chi-square test). For superficial epithelial lesions, the rate of en bloc resection in EMR-C was 96.0% (24 in 25 lesions), which was significantly higher than that in EMR (vs. 68.4%, 13 in 19 lesions; p Z 0.0139, chi-square test). Furthermore, no significant difference in the mean size of the resected superficial epithelial type of SNADA was observed between EMR-C and EMR (7.6 3.2 mm vs. 8.7 4.3 mm; p Z 0.361, MannWhitney U test). Conclusions: EMR-C had a significant higher rate of en bloc resection of the superficial epithelial type of SNADA than EMR. EMR-C is a safe and effective treatment of SNADA, especially of the superficial epithelial type.
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BACKGROUND We recently demonstrated that the odds of contracting coronavirus disease 2019 (COVID-19) in patients with celiac disease (CeD) is similar to that of the general population. However, how patients with CeD perceive their... more
BACKGROUND We recently demonstrated that the odds of contracting coronavirus disease 2019 (COVID-19) in patients with celiac disease (CeD) is similar to that of the general population. However, how patients with CeD perceive their COVID-19 risk may differ from their actual risk. AIM To investigate risk perceptions of contracting COVID-19 in patients with CeD and determine the factors that may influence their perception. METHODS We distributed a survey throughout 10 countries between March and June 2020 and collected data on demographics, diet, COVID-19 testing, and risk perceptions of COVID-19 in patients with CeD. Participants were recruited through various celiac associations, clinic visits, and social media. Risk perception was assessed by asking individuals whether they believe patients with CeD are at an increased risk of contracting COVID-19 when compared to the general population. Logistic regression was used to determine the influencing factors associated with COVID-19 risk perception, such as age, sex, adherence to a gluten-free diet (GFD), and comorbidities such as cardiac conditions, respiratory conditions, and diabetes. Data was presented as adjusted odds ratios (aORs) RESULTS A total of 10737 participants with CeD completed the survey. From them, 6019 (56.1%) patients with CeD perceived they were at a higher risk or were unsure if they were at a higher risk of contracting COVID-19 compared to the non-CeD population. A greater proportion of patients with CeD perceived an increased risk of contracting COVID-19 when compared to infections in general due to their CeD (56.1% vs 26.7%, P < 0.0001). Consequently, 34.8% reported taking extra COVID-19 precautions as a result of their CeD. Members of celiac associations were less likely to perceive an increased risk of COVID-19 when compared to non-members (49.5% vs 57.4%, P < 0.0001). Older age (aOR: 0.99; 95%CI: 0.99 to 0.99, P < 0.001), male sex (aOR: 0.84; 95%CI: 0.76 to 0.93, P = 0.001), and strict adherence to a GFD (aOR: 0.89; 95%CI: 0.82 to 0.96, P = 0.007) were associated with a lower perception of COVID-19 risk and the presence of comorbidities was associated with a higher perception of COVID-19 risk (aOR: 1.38; 95%CI: 1.22 to 1.54, P < 0.001). CONCLUSION Overall, high levels of risk perceptions, such as those found in patients with CeD, may increase an individual’s pandemic-related stress and contribute to negative mental health consequences. Therefore, it is encouraged that public health officials maintain consistent communication with the public and healthcare providers with the celiac community. Future studies specifically evaluating mental health in CeD could help determine the consequences of increased risk perceptions in this population.
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We evaluated 133adult CD patients at diagnosis and 70 healthy controls. Fifty-three patients completed questionnaires every 3 months duringthe first year and more than 4 years after diagnosis. GERDsymptoms were evaluated using a... more
We evaluated 133adult CD patients at diagnosis and 70 healthy controls. Fifty-three patients completed questionnaires every 3 months duringthe first year and more than 4 years after diagnosis. GERDsymptoms were evaluated using a subdimension of the Gastro-intestinal Symptoms Rating Scale for heartburn and regurgita-tion domains.
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To evaluate the ability of interleukin (IL)-15 to control T cell functions through its influence on CD30 and OX40 expressing cells in Celiac Disease (CD). In peripheral blood (PB), by examining the expression of OX40 in conventional... more
To evaluate the ability of interleukin (IL)-15 to control T cell functions through its influence on CD30 and OX40 expressing cells in Celiac Disease (CD). In peripheral blood (PB), by examining the expression of OX40 in conventional effectors cells and T cells with a phenotypic specialization of regulatory cells [CD4+CD25high forkhead box protein 3 (Foxp3)+], and the co stimulation of IFN-γ and IL-4 production within CD30 and OX40 positive subsets of T cells. At the duodenal mucosa, by assessing the expression of CD30 and OX40 in intraepithelial (IE) and lamina propria (LP) lymphocytes (IEL, LPL). PB and duodenal mucosal biopsies were obtained from 38 patients with classic CD (Cel) and 38 healthy controls (HC). Analysis of cell surface and/or intracellular antigens was performed in anti-CD3-treated PB mononuclear cells (PBMC) before and after treatment with recombinant IL-15 (rIL-15), and in IE and LP cellular suspensions prepared from duodenal biopsies pre-treated with/without rIL-15. A subpopulation of CD3+OX40+ T blasts was induced in Cel and HC by a 3days treatment of PBMC with anti-CD3 and decreased its size thereafter, regardless of the presence of rIL-15. However, the addition of rIL-15 to T blasts distinctively induced the survival of T cells with a regulatory phenotype that expresses OX40 antigen in Cel (p&amp;amp;lt;0.05). Celiac patients showed higher frequencies of IFN-γ-producing CD3+CD30+ blasts before and after treatment with rIL-15 (p&amp;amp;lt;0.05, vs. HC). IL-15 increased the frequencies of CD3+CD30+ LPL (HC: p&amp;amp;lt;0.05, Cel: p&amp;amp;lt;0.05) but not of CD3+OX40+ LPL, and CD30 or OX40 positive IEL. The distinctive control of OX40+ cells with a T regulatory phenotype mediated by the influence of IL-15 comes out as new function of this cytokine in the context of CD. The higher production of IFN-γ by a subpopulation of peripheral CD3+CD30+ cells contributes to the type I biased immune response.
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Research Interests: Biomedical Engineering, Bone Metabolism, Medicine, Osteoporosis, Humans, and 15 moreCeliac Disease, Female, Disease, Male, Bone Density, Calcified tissue, Clinical Sciences, North America, Bone remodeling, Bone Formation, Genetic Susceptibility, Biochemistry and cell biology, Gluten Free Diet, Gluten Free, and Bone mass
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One hundred and thirty-two different intestinal alpha 1-antitrypsin clearance tests were performed in 48 untreated adult celiac patients, 64 patients taking a gluten-free diet, and 20 adult healthy controls. In the untreated group, 95% of... more
One hundred and thirty-two different intestinal alpha 1-antitrypsin clearance tests were performed in 48 untreated adult celiac patients, 64 patients taking a gluten-free diet, and 20 adult healthy controls. In the untreated group, 95% of patients had enteric protein loss with values higher than the upper limit of normality (mean +/- 2 SD). In the treated group of patients, only 22% had abnormal levels of alpha 1-antitrypsin clearance. Sixteen patients who had elevated clearance before treatment had decreased clearance after an average of 7.4 months on a gluten-free diet. There was a significant relation (p less than 0.05) between the alpha 1-antitrypsin clearance and the degree of alteration of the jejunal histological structure. We conclude that enteric protein loss is a very frequent finding in celiac patients and the measurement of alpha 1-antitrypsin clearance may be a reliable method to evaluate the activity of the disease and useful in following the efficacy of treatment.
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Nitric oxide is thought to play an important role in modulating chronic inflammatory responses as well as in immune-mediated inflammation. We reproduced a gluten-mediated mucosal response in the rectum of celiac and control subjects in... more
Nitric oxide is thought to play an important role in modulating chronic inflammatory responses as well as in immune-mediated inflammation. We reproduced a gluten-mediated mucosal response in the rectum of celiac and control subjects in order to determine the role of inducible and constitutive nitric oxide synthases in the pathogenesis of this process. Nine patients with confirmed celiac disease and five healthy controls underwent a long-term rectal gluten challenge (48 h) after an enema of 6 g of crude gluten, and constitutive and inducible nitric oxide synthase activity were determined in rectal biopsies. The histological localization of inducible nitric oxide synthase was determined by immunohistochemistry. Activity of both isoforms of nitric oxide synthase in control subjects did not change significantly after gluten instillation. In celiac patients, constitutive nitric oxide synthase on rectal mucosa also showed no significant changes after challenge with gluten. Inducible nitric oxide synthase isoform exhibited a modest increase 4 h after gluten instillation in celiac patients (mean increase 35% compared with baseline levels) but, 8 h after challenge, generation of iNO synthase was significantly higher: 54% more than pre-challenge production (P &lt; 0.05) and higher than control values (P &lt; 0.05). Inducible nitric oxide synthase staining was mostly localized in mononuclear cells of the epithelium and the lamina propria. After gluten instillation, the enhanced staining was mainly localized in subepithelial areas of the lamina propria. Our data suggest a role for nitric oxide, generated by inducible nitric oxide synthase, in the process of rectal mucosa injury by local gluten instillation in sensitized patients. We could not, however, determine if the role of nitric oxide in the ensuing injury of this gluten-induced immune inflammation model is a protective one, or merely a by-product generated by the activation of the inflammatory cells.
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Interleukin (IL)-15 and CD30 may be associated with the ongoing intestinal immunologic activation in celiac disease (CD). We studied duodenal biopsies and blood samples of patients with active CD (Cel) and controls in order to determine... more
Interleukin (IL)-15 and CD30 may be associated with the ongoing intestinal immunologic activation in celiac disease (CD). We studied duodenal biopsies and blood samples of patients with active CD (Cel) and controls in order to determine the regulatory role proposed for CD30(+) T cells in this Th1-driven disease and the potential influences of IL-15 on CD30 expression. We detected that a CD30(+) T-cell subpopulation persists longer in Cel after a 5 day incubation with anti-CD3 antibody than in controls (p = 0.0063). CD30 upregulation by IL-15 in T blasts was greater in Cel than in controls (p = 0.0062). At the mucosal compartment, the CD30 antigen was examined by immunohistochemistry and quantified on isolated lamina propria (LP) and epithelial T cells by flow cytometry. For Cel and controls, similar mean percentages of CD3(+)CD30(+) intraepithelial T cells (5.88 vs. 5.51, p = ns) and LP T cells (7.38 vs. 7.49, p = ns) were observed at baseline and after in vitro gliadin challenge of duodenal biopsy samples. Our study demonstrates the occurrence of potentially important alterations of the immune response at the peripheral compartment. Our findings also allow us to speculate that a negative effect of soluble mediators at the mucosal compartment might counteract the latent influence of IL-15 on CD30 expression precluding a more severe course of active CD.
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A New Model to Predict Survival in Patients with Refractory Celiac Disease (MRCD): Results from a Multinational Study Alberto Rubio-Tapia, MD,1 Georgia Malamut, MD, PhD,2 Wieke Verbeek, MD, PhD,3 Daniel Leffl er, MD, MS,4 Sonia Niveloni,... more
A New Model to Predict Survival in Patients with Refractory Celiac Disease (MRCD): Results from a Multinational Study Alberto Rubio-Tapia, MD,1 Georgia Malamut, MD, PhD,2 Wieke Verbeek, MD, PhD,3 Daniel Leffl er, MD, MS,4 Sonia Niveloni, MD,5 Carolina ArguellesGrande, MD,6 Joseph Murray, MD,1 Brian Lahr, MS,1 Ciaran Kelly, MD,4 Julio Bai, MD,5 Peter Green, MD,6 Severin Daum, MD, PhD,7 Chris Mulder, MD, PhD,3 Christophe Cellier, MD, PhD2. 1. Gastroenterology and Hepatology, Mayo Clinic, Rochester, MN; 2. Hopital Europeen Georges Pompidou, Paris, France; 3. VU University Medical Centre, Amsterdam, Netherlands; 4. Beth Israel Deaconess Medical Center, Boston, MA; 5. Hospital Dr. Carlos Bonorino Udaondo, Buenos Aires, Argentina; 6. Columbia University Medical Center, New York, NY; 7. Charite University Medicine Berlin, Berlin, Germany.