- Email: [email protected]
Sa1258 Risk of Cardiovascular Disease in Individuals With Celiac Disease
AGA Abstracts
lesions in the duodenum mucosa. The typical manifestation is distinguished by gastrointestinal symptoms such as diarrhoea, vomiting, abdominal distension and failure to thrive. On the other hand atypical forms are characterized by extraintestinal symptoms (anemia, low height, delayed puberty, headaches). The aim of our study was to perform a CD screening in school-age children in order to obtain a timely diagnosis of the disease that might permit a propter growth and to compare the compliance and clinical appearance of the disease in three different cohorts: A big metropolis (Rome), a small mountain city (L'Aquila) and a small seaside city (Civitavecchia). Salivary samples were collected and tested for antitransglutaminase antibodies (tTGAb) using a fluid-phase radioimmunoprecipitation method. Subjects salivary tTGAb-positive were subsequently tested for serum CD-specific antibodies (RIA tTGAb and ELISA tTGAb). Confirmed positive children underwent endoscopy with multiple duodenal biopsies, and at CD diagnosis, started a gluten-free diet. The study was performed on: Group 1: 5733 out of 7377 school-children who were invited to participate in the city of Rome; Group 2: 751 out of 954 school-children who were invited to participate in the city of L'Aquila; Group 3: 816 out of 1004 school-children who were invited to participate in the city of Civitavecchia. The celiac children were: Group 1: 68 (45 newly diagnosed and 23 already celiacs), Group 2: 13 (7 newly diagnosed and 6 already celiacs), Group 3: 11 (8 newly diagnosed and 3 already celiacs). The CD prevalence in the three groups investigated were: Group 1: 1.2%, Group 2: 1.7% Group 3: 1.3%. The figure shows the clinical pictures of the three groups. In conclusion, our study demonstrates the high compliance of the parents and of the children to the salivary test. CD prevalence is higher than expected, particularly in group 2 children, with a modified clinical spectrum. CD iceberg is still deep, hence, the salivary tTGAb, that is a non-invasive, simple, reproducible and sensitive screening method has proved to be a powerful tool in identifying celiac children.
Sa1256 High-Resolution Peripheral Quantitative Computerized Tomography Demonstrates Characteristics of Bone Fragility in Active Celiac Disease Patients Maria B. Zanchetta, Roberto M. Mazure, Vanesa Longobardi, Edgardo Smecuol, Gabriela I. Longarini, Ana F. Costa, Horacio Vázquez, Sonia I. Niveloni, María Laura Moreno, Hwang Hui Jer, Eduardo Mauriño, Julio C. Bai Backgrounds: Patients with active celiac disease (CD) are more likely to have osteoporosis and increased risk for bone fractures. Cole's fracture is the most common event in CD patients (54%). Assessment of patients' risk using bone mineral densitometry (BMD) is recommended by CD guidelines. However, BMD does not always represent a precise indicator of damage and a reliable predictor of bone fracture. High-resolution peripheral quantitative computed tomography (HR-pQCT) is a new in vivo imaging technique for assessing 3D microstructure of cortical and trabecular bone and for giving inside to factors involved in bone fragility. To our knowledge, no studies have investigated microstructural quality of bones in CD patients. Aims: To determine the structure characteristics of peripheral bones in a consecutive cohort of adult pre-menopausal females with active CD assessed at the time of diagnosis by using HR-pQCT. Methods: We prospectively enrolled 30 consecutive female patients with newly diagnosed CD. Parameters of patients were compared with 30 healthy, age-matched females with normal BMD measurements (lumbar spine, femoral neck and ultradistal radius). HR-pQCT bone volumetric and structural measurements were determined at the ultradistal non-dominant radius and tibia. Results: CD patients and healthy controls were comparable in terms of age, height, weight and body mass index (pNS). Lumbar spine, femoral neck and ultradistal radius BMD of CD patients were significantly lower than those values determined for healthy controls (p,0.01; p,0.04, p,0.001; respectively). However, while mean lumbar spine and femoral neck BMD values for CD patients remained in the normal range, ultradistal radius BMD mean z-score value for patients (-1.9±1.2) was borderline the lower end of the range expected for age. Structural damage in patients measured by using HR-pQCT was considerably higher in the ultradistal radius compared with tibia. Compared with controls, CD patients were significantly affected in the total volumetric density (p,0.006), trabecular density (p ,0.001), bone volume/trabecular volume ratio (p,0.001), number of trabecules/mm (p,0.001) and trabecular thickness (p,0.004). Cortical bone was not significantly affected in any of the areas assessed. Conclusions: HR-pQCT was able to identify significant bone trabecular deterioration that may be responsible for the increased fragility and fracture prevalence in active CD. This affected quality of the trabecular bone was characterized by a lower number and a reduced thickness of trabecules, both producing a lower trabecular density. These changes were more pronounced in the ultradistal radius. Notably, cortical bone was preserved. Whether these women are able to recover trabecular bone density and structure after gluten-free diet is not known and will be assess in future results of this longitudinal study.
Sa1258 Risk of Cardiovascular Disease in Individuals With Celiac Disease Rohini R. Vanga, Toufic A. Kabbani, Rupa Mukherjee, Javier A. Villafuerte-Galvez, Kumar Pallav, Melinda Dennis, Ciaran P. Kelly, Daniel A. Leffler Background: Cardiovascular disease (CVD) is a major public health problem in the United States and worldwide. Population data from Europe and Sweden in particular suggests that CVD is the most common cause of death in individuals with celiac disease (CD) followed by malignancy. Modifiable risk factors for CVD including body mass index and cholesterol have been shown to increase on a gluten free diet (GFD) in patients with CD and the prevalence of Type 1 diabetes is high in CD compared to general population. Conversely, CD is associated with lower risks of Type 2 diabetes and metabolic syndrome. Little is known however about overall CVD risk factors in the celiac population. The aim of this study is to assess the overall risk of CVD in adults with CD compared to the general population and how CVD risk changes on treatment with the GFD. Methods: Chart review was performed for 155 individuals with CD, and age, ethnicity and gender matched controls. Data on age, gender, systolic blood pressure (SBP) and treatment for hypertension, total cholesterol, HDL cholesterol, smoking and DM (type I or II) status were collected. For the CD population, data were collected at the time of initial diagnosis and at their most recent follow up visit. The10 year Framingham Risk Score for general CVD was calculated for men and women separately using the 2008 Framingham Heart Study predictive model. Student's T test and Fischer's exact test were used for statistical analysis. Results: A total of 155 individuals with CD (45 (29%) men and 110 (71%) women) and matched controls were identified. 92% of the study population was caucasian. The mean age of CD diagnosis was 51.4 years in men and 48.2 years in women. Average length of time on GFD was 72.6 months in men and 68.4 months in women. The 10 year risk for general CVD in men with CD at diagnosis was 10.9% vs.12.9% in controls, p = 0.410. In women with CD the 10 year CVD risk was 5.3% vs 5.1% in controls, p = 0.778. After treatment with a GFD the 10 year CVD risk for men with CD was 14.5% vs. 19.7% in controls, p = 0.086. The 10 year CVD risk for women with CD on a GFD was 6.1% vs. 6.29% in controls, p = 0.8. The difference in CVD risk between individuals with CD at diagnosis and on a GFD was attributable to the increased age of the treated CD population. Data on individual risk factors between celiac disease and their matched controls is demonstrated in Tables 1&2. Conclusions: A trend towards decreased general cardiovascular disease risk in men with celiac disease, as calculated by the Framingham Risk Score compared to matched controls was observed in our study, although this did not reach statistical significance in the current sample size. Overall, our data suggest that CVD risk is not increased in the celiac population and that treatment with the gluten free diet does not increase CVD risk. Risk of cardiovascular disease in men with celiac disease compared to matched controls
Sa1257 Celiac Disease Salivary Screening in Italy: Prevalence and Clinical Pictures of the Disease Raffaella Nenna, Claudio Tiberti, Laura Petrarca, Arianna Turchetti, Maurizio Mennini, Rita Pia Lara Luparia, Matteo Florio, Nicoletta Pietropaoli, Monica Montuori, Mirka Guido, Gerarda Mastrogiorgio, Federica Lucantoni, Teresa Gentile, Maria Bavastrelli, Margherita Bonamico Celiac disease (CD) is a chronic autoimmune pathology, caused by a permanent intolerance to gluten contained in wheat and to similar prolamines present in barley and rye. It is a common disease as its prevalence, in Caucasian populations, is about 1%. There are several patterns of MC: symptomatic CD, and silent CD, both characterized by typical histological
AGA Abstracts
S-244
Sa1260
Background: Glutens are the major storage proteins of wheat and related cereals, comprising over 70 different molecules in any given wheat variety. Elevated IgG and IgA antibody response to gluten proteins is associated with celiac disease (CD), dermatitis herpetiformis (DH), and non-celiac gluten sensitivity. However, antigenic specificity of the immune response to gluten and non-gluten proteins of wheat has not been systematically examined in the context of non-responsive CD, non-celiac gluten sensitivity, or patient response to diet in typical CD or DH. The aim of this study was to develop a novel proteomic microarray system to accurately map the molecular specificity of the antibody response to wheat proteins in gluten-related disorders. Methods: Gluten and non-gluten proteins were separately extracted from two varieties of wheat, Cheyenne and Butte 86. The proteins were separated by reversed-phase high performance liquid chromatography (RP-HPLC). In addition, gluten proteins were digested with pepsin/trypsin/chymotrypsin, followed by RP-HPLC separation. Over 570 collected fractions were lyophilized, re-dissovled in printing buffer, and printed in duplicate on nitrocellulose-coated glass slides. Prepared microarrays were brought into contact with diluted serum samples from patients with CD (n=10) and DH (n=3), as well as healthy controls (n=10). The arrays were washed and incubated with Alexa647-labled anti-human IgG and Cy3-labeled anti-human IgA antibodies, and scanned with a GenePix 4000B Axon instrument for simultaneous acquisition of IgG and IgA antibody data at 635 nm and 532 nm. Data were analyzed using the GenePix Pro 6.0 software. Results: The generated data revealed unique patterns of antibody reactivity to the printed protein and peptide spots when comparing CD and DH patients to healthy controls. The array system was capable of high sensitivity detection of antibody reactivity to the various gluten protein chromatographic fractions, including α/β-gliadins, γ-gliadins, ω-gliadins, high molecular weight glutenins, and low molecular weight glutenins, as well as gluten peptides and nongluten proteins. Conclusion: The results demonstrated the utility and power of the constructed microarray system for accurately mapping the antigenic specificity of the immune response to wheat proteins in CD and other gluten-related disorders. Better characterization and mapping of the antibody response profile in affected patients has the potential to yield useful biomarkers and novel clues regarding mechanism.
Risk of cardiovascular disease in women with celiac disease compared to matched controls
Sa1261 A Quantitative Assessment of Psychological Distress in Celiac Disease Patients At the Time of Diagnosis Cristina Sfoggia, Fabio Nachman, Edgardo Smecuol, María Laura Moreno, Horacio Vázquez, Andrea F. Gonzalez, Paola J. Andrenacci, Sonia I. Niveloni, Roberto M. Mazure, Hwang Hui Jer, Emilia Sugai, Maria Ines Pinto Sanchez, Eduardo Mauriño, Julio C. Bai INTRODUCTION: There is growing interest in knowing about mood disorders of patients with celiac disease (CD). However, little is known about the psychological distress of patients before treatment and how this perception is related with the clinical presentation of the disease. AIMS: Our objectives in this cross-sectional prospective study were: 1- to determine the level of psychological morbidity in a cohort of CD patients assessed at the time of diagnosis; and 2- to establish psychological characteristics of patients according to the clinical categorization at presentation. PATIENTS/METHODS: We enrolled 128 consecutive adult patients with newly diagnosed CD (110 female; median age: 35 yr). At diagnosis, 95 patients were categorized as having symptomatic CD (intestinal and extra-intestinal symptoms) and 33 were considered as having subclinical CD. We employed the Symptom Checklist-90 Revised (SCL-90-R) questionnaire which is a self-report symptom inventory to measure psychological distress in terms of nine primary symptom dimensions and three global indices; one of these, the global severity index (GSI) reflects the overall severity of all symptoms. Those with a GSI or any two primary dimensions score greater than or equal to a T score of 63 (percentile 90) were considered at high risk for a psychiatric diagnosis. Baseline scores were compared with values reported for the Buenos Aires city population. RESULTS: Compared with the local general population, 8/9 and 4/9 dimensions and the GSI were significantly impaired in female and male with untreated CD, respectively (p ,0.05 to p,0.0001). Female patients with a symptomatic clinical presentation were the most affected population having 6/9 dimensions significantly impaired compared with subclinical CD cases (p,0.01 to p,0.0001). The most affected dimensions were: somatization and the GSI (p,0.0001), psychoticism (p,0.002); depression (p,0.009); and hostility, anxiety and paranoid ideations (p,0.01). When individual values were considered according to the normalized T-score, 35% of patients had criteria for being considered at high risk of psychiatric diagnosis. Once again, this risk was strongly associated with the symptomatic clinical presentation (p,0.0001 for all dimensions). Furthermore, scores for all dimensions of the SCL-90-R in subclinical CD patients did not differ from those for controls. CONCLUSIONS: Our study shows that patients with untreated CD have increased psychological morbidity compared with the general population. The psychological distress was significantly associated with the symptomatic clinical presentation. Contrarily, patients with subclinical CD were not affected in their psychological behavior
Sa1259 How Often Do Hematologists Screen for Celiac Disease? Scott M. Smukalla, Benjamin Lebwohl, John Gregory Mears, Lori A. Leslie, Peter H. Green Background: Celiac disease (CD) is associated with significant morbidity and mortality and is considered to be under-diagnosed in the United States. Iron deficiency anemia (IDA) is an increasingly recognized presentation of CD. There are no guidelines in the literature for screening for CD among those with IDA in the US. We therefore surveyed practicing hematologists to determine rates of CD screening in patients diagnosed with IDA. Methods: A survey was developed by four gastroenterologists, a hematologist, and two medical residents. It was tested on hematologists for content and ease of use. It was submitted via surveymonkey.com and emailed to members of the American Society of Hematology. Questions included demographics, workup of hypothetical patients, and agree/disagree statements. We constructed a multivariate model to assess for independent associations between years in practice, subspecialty, patient volume, and patient age on providers' attitudes regarding screening for CD. The dependent variable was the response "agree" or "strongly agree" to the statement "all patients with IDA should have celiac serologies sent." Results: There were 385 complete responses from 4551 emails for a response rate of 8.5%. Most respondents were practicing clinicians (76%), followed by clinical researchers (10%), and laboratory researchers (6%). Benign hematologists accounted for 45% of respondents, followed by oncologists (33%) and malignant hematologists (22%). The most common practice types were university-affiliated hospital (43%), private clinic (29%), community hospital (12%), and VA hospital (9%). Most respondents saw an average of 3-5 (31%) or 6-10 (28%) patients with IDA per month, with an average patient age of 31-50 (47%) followed by 51-70 (34%). In the evaluation of hypothetical patients with IDA, only 18% were likely to test for CD in 45 year old premenopausal women, while 12% would test 55 year old postmenopausal women. Only 8.6% of respondents believe that all patients with IDA should be screened for CD. Respondents with 0-5 years in practice since completion of training were more likely than all other respondents to screen for CD (16% vs 7%, OR=2.4, p=0.05). Higher volumes of IDA patients per month also significantly increased the likelihood of screening for CD (OR 5.6, p=0.01). In multivariate analysis, both malignant hematologists (OR 3.2, CI 1.1-9.5, p=0.04) and oncologists (OR 3.5, CI 1.3-9.5, p=0.02) were more likely than benign hematologists to screen all patients for CD, as were those who saw predominately pediatric patients with IDA versus adult patients (OR 16.9, CI 3.0-97.0, p=0.002). Conclusions: Practicing hematologists infrequently screen for CD in patients with IDA. Physicians that have recently finished fellowship are more likely to screen for CD as are those who see a high volume of patients with IDA.
Sa1262 A New Prognostic Model for Enteropathy Associated T-Cell Lymphoma Laura R. de Baaij, Jolanda M. van de Water, Michal K. Sieniawski, Marijn Radersma, Wieke H. Verbeek, Otto Visser, Johannes Berkhof, Joost J. Oudejans, Chris J. Meijer, Chris J. Mulder, Anne L. Lennard, Saskia A. Cillessen Enteropathy-Associated T-cell Lymphoma (EATL) is a rare intestinal non-Hodgkin lymphoma which is often associated with adult-onset celiac disease (CD). EATL can be clinically divided into two subtypes: primary and secondary EATL. Primary EATL develops without a preceding history of CD. The first presentation is often perforation or obstruction, which leads to diagnosis of both EATL and CD. Secondary EATL is diagnosed in patients with wellestablished CD or refractory CD. These patients deteriorate and eventually develop EATL.
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AGA Abstracts
AGA Abstracts
A Microarray System for Proteomic Analysis of the Immune Response to Wheat Proteins in Celiac Disease and Gluten Sensitivity Sina Moeller, Donald D. Kasarda, Peter H. Green, Armin Alaedini
lesions in the duodenum mucosa. The typical manifestation is distinguished by gastrointestinal symptoms such as diarrhoea, vomiting, abdominal distension and failure to thrive. On the other hand atypical forms are characterized by extraintestinal symptoms (anemia, low height, delayed puberty, headaches). The aim of our study was to perform a CD screening in school-age children in order to obtain a timely diagnosis of the disease that might permit a propter growth and to compare the compliance and clinical appearance of the disease in three different cohorts: A big metropolis (Rome), a small mountain city (L'Aquila) and a small seaside city (Civitavecchia). Salivary samples were collected and tested for antitransglutaminase antibodies (tTGAb) using a fluid-phase radioimmunoprecipitation method. Subjects salivary tTGAb-positive were subsequently tested for serum CD-specific antibodies (RIA tTGAb and ELISA tTGAb). Confirmed positive children underwent endoscopy with multiple duodenal biopsies, and at CD diagnosis, started a gluten-free diet. The study was performed on: Group 1: 5733 out of 7377 school-children who were invited to participate in the city of Rome; Group 2: 751 out of 954 school-children who were invited to participate in the city of L'Aquila; Group 3: 816 out of 1004 school-children who were invited to participate in the city of Civitavecchia. The celiac children were: Group 1: 68 (45 newly diagnosed and 23 already celiacs), Group 2: 13 (7 newly diagnosed and 6 already celiacs), Group 3: 11 (8 newly diagnosed and 3 already celiacs). The CD prevalence in the three groups investigated were: Group 1: 1.2%, Group 2: 1.7% Group 3: 1.3%. The figure shows the clinical pictures of the three groups. In conclusion, our study demonstrates the high compliance of the parents and of the children to the salivary test. CD prevalence is higher than expected, particularly in group 2 children, with a modified clinical spectrum. CD iceberg is still deep, hence, the salivary tTGAb, that is a non-invasive, simple, reproducible and sensitive screening method has proved to be a powerful tool in identifying celiac children.
Sa1256 High-Resolution Peripheral Quantitative Computerized Tomography Demonstrates Characteristics of Bone Fragility in Active Celiac Disease Patients Maria B. Zanchetta, Roberto M. Mazure, Vanesa Longobardi, Edgardo Smecuol, Gabriela I. Longarini, Ana F. Costa, Horacio Vázquez, Sonia I. Niveloni, María Laura Moreno, Hwang Hui Jer, Eduardo Mauriño, Julio C. Bai Backgrounds: Patients with active celiac disease (CD) are more likely to have osteoporosis and increased risk for bone fractures. Cole's fracture is the most common event in CD patients (54%). Assessment of patients' risk using bone mineral densitometry (BMD) is recommended by CD guidelines. However, BMD does not always represent a precise indicator of damage and a reliable predictor of bone fracture. High-resolution peripheral quantitative computed tomography (HR-pQCT) is a new in vivo imaging technique for assessing 3D microstructure of cortical and trabecular bone and for giving inside to factors involved in bone fragility. To our knowledge, no studies have investigated microstructural quality of bones in CD patients. Aims: To determine the structure characteristics of peripheral bones in a consecutive cohort of adult pre-menopausal females with active CD assessed at the time of diagnosis by using HR-pQCT. Methods: We prospectively enrolled 30 consecutive female patients with newly diagnosed CD. Parameters of patients were compared with 30 healthy, age-matched females with normal BMD measurements (lumbar spine, femoral neck and ultradistal radius). HR-pQCT bone volumetric and structural measurements were determined at the ultradistal non-dominant radius and tibia. Results: CD patients and healthy controls were comparable in terms of age, height, weight and body mass index (pNS). Lumbar spine, femoral neck and ultradistal radius BMD of CD patients were significantly lower than those values determined for healthy controls (p,0.01; p,0.04, p,0.001; respectively). However, while mean lumbar spine and femoral neck BMD values for CD patients remained in the normal range, ultradistal radius BMD mean z-score value for patients (-1.9±1.2) was borderline the lower end of the range expected for age. Structural damage in patients measured by using HR-pQCT was considerably higher in the ultradistal radius compared with tibia. Compared with controls, CD patients were significantly affected in the total volumetric density (p,0.006), trabecular density (p ,0.001), bone volume/trabecular volume ratio (p,0.001), number of trabecules/mm (p,0.001) and trabecular thickness (p,0.004). Cortical bone was not significantly affected in any of the areas assessed. Conclusions: HR-pQCT was able to identify significant bone trabecular deterioration that may be responsible for the increased fragility and fracture prevalence in active CD. This affected quality of the trabecular bone was characterized by a lower number and a reduced thickness of trabecules, both producing a lower trabecular density. These changes were more pronounced in the ultradistal radius. Notably, cortical bone was preserved. Whether these women are able to recover trabecular bone density and structure after gluten-free diet is not known and will be assess in future results of this longitudinal study.
Sa1258 Risk of Cardiovascular Disease in Individuals With Celiac Disease Rohini R. Vanga, Toufic A. Kabbani, Rupa Mukherjee, Javier A. Villafuerte-Galvez, Kumar Pallav, Melinda Dennis, Ciaran P. Kelly, Daniel A. Leffler Background: Cardiovascular disease (CVD) is a major public health problem in the United States and worldwide. Population data from Europe and Sweden in particular suggests that CVD is the most common cause of death in individuals with celiac disease (CD) followed by malignancy. Modifiable risk factors for CVD including body mass index and cholesterol have been shown to increase on a gluten free diet (GFD) in patients with CD and the prevalence of Type 1 diabetes is high in CD compared to general population. Conversely, CD is associated with lower risks of Type 2 diabetes and metabolic syndrome. Little is known however about overall CVD risk factors in the celiac population. The aim of this study is to assess the overall risk of CVD in adults with CD compared to the general population and how CVD risk changes on treatment with the GFD. Methods: Chart review was performed for 155 individuals with CD, and age, ethnicity and gender matched controls. Data on age, gender, systolic blood pressure (SBP) and treatment for hypertension, total cholesterol, HDL cholesterol, smoking and DM (type I or II) status were collected. For the CD population, data were collected at the time of initial diagnosis and at their most recent follow up visit. The10 year Framingham Risk Score for general CVD was calculated for men and women separately using the 2008 Framingham Heart Study predictive model. Student's T test and Fischer's exact test were used for statistical analysis. Results: A total of 155 individuals with CD (45 (29%) men and 110 (71%) women) and matched controls were identified. 92% of the study population was caucasian. The mean age of CD diagnosis was 51.4 years in men and 48.2 years in women. Average length of time on GFD was 72.6 months in men and 68.4 months in women. The 10 year risk for general CVD in men with CD at diagnosis was 10.9% vs.12.9% in controls, p = 0.410. In women with CD the 10 year CVD risk was 5.3% vs 5.1% in controls, p = 0.778. After treatment with a GFD the 10 year CVD risk for men with CD was 14.5% vs. 19.7% in controls, p = 0.086. The 10 year CVD risk for women with CD on a GFD was 6.1% vs. 6.29% in controls, p = 0.8. The difference in CVD risk between individuals with CD at diagnosis and on a GFD was attributable to the increased age of the treated CD population. Data on individual risk factors between celiac disease and their matched controls is demonstrated in Tables 1&2. Conclusions: A trend towards decreased general cardiovascular disease risk in men with celiac disease, as calculated by the Framingham Risk Score compared to matched controls was observed in our study, although this did not reach statistical significance in the current sample size. Overall, our data suggest that CVD risk is not increased in the celiac population and that treatment with the gluten free diet does not increase CVD risk. Risk of cardiovascular disease in men with celiac disease compared to matched controls
Sa1257 Celiac Disease Salivary Screening in Italy: Prevalence and Clinical Pictures of the Disease Raffaella Nenna, Claudio Tiberti, Laura Petrarca, Arianna Turchetti, Maurizio Mennini, Rita Pia Lara Luparia, Matteo Florio, Nicoletta Pietropaoli, Monica Montuori, Mirka Guido, Gerarda Mastrogiorgio, Federica Lucantoni, Teresa Gentile, Maria Bavastrelli, Margherita Bonamico Celiac disease (CD) is a chronic autoimmune pathology, caused by a permanent intolerance to gluten contained in wheat and to similar prolamines present in barley and rye. It is a common disease as its prevalence, in Caucasian populations, is about 1%. There are several patterns of MC: symptomatic CD, and silent CD, both characterized by typical histological
AGA Abstracts
S-244
Sa1260
Background: Glutens are the major storage proteins of wheat and related cereals, comprising over 70 different molecules in any given wheat variety. Elevated IgG and IgA antibody response to gluten proteins is associated with celiac disease (CD), dermatitis herpetiformis (DH), and non-celiac gluten sensitivity. However, antigenic specificity of the immune response to gluten and non-gluten proteins of wheat has not been systematically examined in the context of non-responsive CD, non-celiac gluten sensitivity, or patient response to diet in typical CD or DH. The aim of this study was to develop a novel proteomic microarray system to accurately map the molecular specificity of the antibody response to wheat proteins in gluten-related disorders. Methods: Gluten and non-gluten proteins were separately extracted from two varieties of wheat, Cheyenne and Butte 86. The proteins were separated by reversed-phase high performance liquid chromatography (RP-HPLC). In addition, gluten proteins were digested with pepsin/trypsin/chymotrypsin, followed by RP-HPLC separation. Over 570 collected fractions were lyophilized, re-dissovled in printing buffer, and printed in duplicate on nitrocellulose-coated glass slides. Prepared microarrays were brought into contact with diluted serum samples from patients with CD (n=10) and DH (n=3), as well as healthy controls (n=10). The arrays were washed and incubated with Alexa647-labled anti-human IgG and Cy3-labeled anti-human IgA antibodies, and scanned with a GenePix 4000B Axon instrument for simultaneous acquisition of IgG and IgA antibody data at 635 nm and 532 nm. Data were analyzed using the GenePix Pro 6.0 software. Results: The generated data revealed unique patterns of antibody reactivity to the printed protein and peptide spots when comparing CD and DH patients to healthy controls. The array system was capable of high sensitivity detection of antibody reactivity to the various gluten protein chromatographic fractions, including α/β-gliadins, γ-gliadins, ω-gliadins, high molecular weight glutenins, and low molecular weight glutenins, as well as gluten peptides and nongluten proteins. Conclusion: The results demonstrated the utility and power of the constructed microarray system for accurately mapping the antigenic specificity of the immune response to wheat proteins in CD and other gluten-related disorders. Better characterization and mapping of the antibody response profile in affected patients has the potential to yield useful biomarkers and novel clues regarding mechanism.
Risk of cardiovascular disease in women with celiac disease compared to matched controls
Sa1261 A Quantitative Assessment of Psychological Distress in Celiac Disease Patients At the Time of Diagnosis Cristina Sfoggia, Fabio Nachman, Edgardo Smecuol, María Laura Moreno, Horacio Vázquez, Andrea F. Gonzalez, Paola J. Andrenacci, Sonia I. Niveloni, Roberto M. Mazure, Hwang Hui Jer, Emilia Sugai, Maria Ines Pinto Sanchez, Eduardo Mauriño, Julio C. Bai INTRODUCTION: There is growing interest in knowing about mood disorders of patients with celiac disease (CD). However, little is known about the psychological distress of patients before treatment and how this perception is related with the clinical presentation of the disease. AIMS: Our objectives in this cross-sectional prospective study were: 1- to determine the level of psychological morbidity in a cohort of CD patients assessed at the time of diagnosis; and 2- to establish psychological characteristics of patients according to the clinical categorization at presentation. PATIENTS/METHODS: We enrolled 128 consecutive adult patients with newly diagnosed CD (110 female; median age: 35 yr). At diagnosis, 95 patients were categorized as having symptomatic CD (intestinal and extra-intestinal symptoms) and 33 were considered as having subclinical CD. We employed the Symptom Checklist-90 Revised (SCL-90-R) questionnaire which is a self-report symptom inventory to measure psychological distress in terms of nine primary symptom dimensions and three global indices; one of these, the global severity index (GSI) reflects the overall severity of all symptoms. Those with a GSI or any two primary dimensions score greater than or equal to a T score of 63 (percentile 90) were considered at high risk for a psychiatric diagnosis. Baseline scores were compared with values reported for the Buenos Aires city population. RESULTS: Compared with the local general population, 8/9 and 4/9 dimensions and the GSI were significantly impaired in female and male with untreated CD, respectively (p ,0.05 to p,0.0001). Female patients with a symptomatic clinical presentation were the most affected population having 6/9 dimensions significantly impaired compared with subclinical CD cases (p,0.01 to p,0.0001). The most affected dimensions were: somatization and the GSI (p,0.0001), psychoticism (p,0.002); depression (p,0.009); and hostility, anxiety and paranoid ideations (p,0.01). When individual values were considered according to the normalized T-score, 35% of patients had criteria for being considered at high risk of psychiatric diagnosis. Once again, this risk was strongly associated with the symptomatic clinical presentation (p,0.0001 for all dimensions). Furthermore, scores for all dimensions of the SCL-90-R in subclinical CD patients did not differ from those for controls. CONCLUSIONS: Our study shows that patients with untreated CD have increased psychological morbidity compared with the general population. The psychological distress was significantly associated with the symptomatic clinical presentation. Contrarily, patients with subclinical CD were not affected in their psychological behavior
Sa1259 How Often Do Hematologists Screen for Celiac Disease? Scott M. Smukalla, Benjamin Lebwohl, John Gregory Mears, Lori A. Leslie, Peter H. Green Background: Celiac disease (CD) is associated with significant morbidity and mortality and is considered to be under-diagnosed in the United States. Iron deficiency anemia (IDA) is an increasingly recognized presentation of CD. There are no guidelines in the literature for screening for CD among those with IDA in the US. We therefore surveyed practicing hematologists to determine rates of CD screening in patients diagnosed with IDA. Methods: A survey was developed by four gastroenterologists, a hematologist, and two medical residents. It was tested on hematologists for content and ease of use. It was submitted via surveymonkey.com and emailed to members of the American Society of Hematology. Questions included demographics, workup of hypothetical patients, and agree/disagree statements. We constructed a multivariate model to assess for independent associations between years in practice, subspecialty, patient volume, and patient age on providers' attitudes regarding screening for CD. The dependent variable was the response "agree" or "strongly agree" to the statement "all patients with IDA should have celiac serologies sent." Results: There were 385 complete responses from 4551 emails for a response rate of 8.5%. Most respondents were practicing clinicians (76%), followed by clinical researchers (10%), and laboratory researchers (6%). Benign hematologists accounted for 45% of respondents, followed by oncologists (33%) and malignant hematologists (22%). The most common practice types were university-affiliated hospital (43%), private clinic (29%), community hospital (12%), and VA hospital (9%). Most respondents saw an average of 3-5 (31%) or 6-10 (28%) patients with IDA per month, with an average patient age of 31-50 (47%) followed by 51-70 (34%). In the evaluation of hypothetical patients with IDA, only 18% were likely to test for CD in 45 year old premenopausal women, while 12% would test 55 year old postmenopausal women. Only 8.6% of respondents believe that all patients with IDA should be screened for CD. Respondents with 0-5 years in practice since completion of training were more likely than all other respondents to screen for CD (16% vs 7%, OR=2.4, p=0.05). Higher volumes of IDA patients per month also significantly increased the likelihood of screening for CD (OR 5.6, p=0.01). In multivariate analysis, both malignant hematologists (OR 3.2, CI 1.1-9.5, p=0.04) and oncologists (OR 3.5, CI 1.3-9.5, p=0.02) were more likely than benign hematologists to screen all patients for CD, as were those who saw predominately pediatric patients with IDA versus adult patients (OR 16.9, CI 3.0-97.0, p=0.002). Conclusions: Practicing hematologists infrequently screen for CD in patients with IDA. Physicians that have recently finished fellowship are more likely to screen for CD as are those who see a high volume of patients with IDA.
Sa1262 A New Prognostic Model for Enteropathy Associated T-Cell Lymphoma Laura R. de Baaij, Jolanda M. van de Water, Michal K. Sieniawski, Marijn Radersma, Wieke H. Verbeek, Otto Visser, Johannes Berkhof, Joost J. Oudejans, Chris J. Meijer, Chris J. Mulder, Anne L. Lennard, Saskia A. Cillessen Enteropathy-Associated T-cell Lymphoma (EATL) is a rare intestinal non-Hodgkin lymphoma which is often associated with adult-onset celiac disease (CD). EATL can be clinically divided into two subtypes: primary and secondary EATL. Primary EATL develops without a preceding history of CD. The first presentation is often perforation or obstruction, which leads to diagnosis of both EATL and CD. Secondary EATL is diagnosed in patients with wellestablished CD or refractory CD. These patients deteriorate and eventually develop EATL.
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AGA Abstracts
AGA Abstracts
A Microarray System for Proteomic Analysis of the Immune Response to Wheat Proteins in Celiac Disease and Gluten Sensitivity Sina Moeller, Donald D. Kasarda, Peter H. Green, Armin Alaedini