Health and Nutrition Examination Survey (NHANES) evaluated study population for anti-tissue transglutaminase antibodies and anti-endomysial antibodies for the first time in 2009-2010. There were no population-based studies describing the characteristics of adults whohad positive antibodies but were not diagnosed to have celiac disease. The primary objectiveof our study is to describe the characteristics of adults serologically positive for anti-tissuetransglutaminase antibodies and anti-endomysial antibodies without a diagnosis of celiacdisease in the United States. Methods: We conducted a secondary data analysis of a cross-sectional sample of adults included in NHANES (2009-2010). We included all adult (18years and older) adults included in NHANES (2009-2010) who are serologically positivefor anti-tissue transglutaminase antibodies and anti-endomysial antibodies. We excludedthose adults who self-reported celiac disease and those who are on gluten-free diet. Weexcluded those with anemia in the past 3 months, previous liver or chronic kidney diseasecondition or any cancer when analyzing the laboratory values. We described the demographiccharacteristics of the study population. We described the continuous variables (serum ferritinlevels, serum folate levels, serum hemoglobin, serum transaminases) using mean (95% CI)among adults with positive serological tests. Results: There were 6380 adults in NHANES2009-2010 study (projected to 226 million in the US). Testing for antibodies was done in5799 adults. We identified 39 adults who were serologically positive (0.7%). We excludedtwo adults with celiac disease that are eating a gluten-free diet. Adults with antibodies werepredominantly women (51%) and non-Hispanic white (73%). Majority of them had healthinsurance (92%). Mean age (SD) of the study population was 47 (17) years. Evaluation oftheir laboratory values shown in Table 1 indicates that at least one-third of adults hadanemia and elevated Alanine Aminotransferase (ALT) levels. The mean (95%CI) laboratoryparameters of those serologically positive is shown in Table 2. Conclusion: We found0.7% of adults in the United States had anti-tissue transglutaminase antibodies and/or anti-endomysial antibodies. One-third of them had anemia and elevated ALT levels.Table 2. Laboratory parameters of those with Anti-Tissue Transglutaminase Antibodies andAnti-Endomysial Antibodies. (Data from NHANES 2009-2010)

Table 1.Laboratory values of adults with anti-endomysial and anti-tissue transglutaminaseantibodies.

Sa1268

The Relationship Between Self-Reported Strict Adherence to a Gluten-FreeDiet and the Ability to Identify Gluten-Containing FoodsJocelyn A. Silvester, Dayna Weiten, Lesley A. Graff, John R. Walker, Donald R. Duerksen

Background: The mainstay of treatment for celiac disease (CD) and dermatitis herpetiformis(DH) is avoidance of dietary gluten. Most patients self-report strict adherence to a gluten-freediet (GFD). Diet review by a trained dietitian may detect unrecognised dietary transgressions;nevertheless, many patients deemed "strictly adherent" to a GFD have ongoing mucosaldamage evident on duodenal biopsy specimens. Aims: To determine whether there is arelationship between self-reported dietary adherence and knowledge regarding gluten-free(GF) foods. Methods: Patients with CD and/or DHwere recruited in specialist clinics, throughthe local celiac support group, and through advertisements in businesses specialising in GFproducts. Participants completed a survey with items pertaining to diagnosis, dietary adher-ence and demographics. GF food knowledge was assessed using a list of common foods tobe categorized as ‘foods allowed', ‘foods not allowed' or ‘foods to question'. The maximumquiz score was 16 (one point for each correct response). Results: Of the 179 patients whocompleted the survey (83% female), 162 had CD, 4 had DH and 13 had both CD and DH.The mean time since diagnosis was 8.4 years (range 0.03 to 47 years). Self-reported strictadherence to a GFD was 56%, with 22% reporting rare accidental gluten ingestion, 7% rareintentional gluten ingestion and 10% trying but not always sure if they were following aGFD. There were 40% with at least one additional dietary restriction, with dairy being the

S-247 AGA Abstracts

most frequent. No participant was able to identify correctly the GF status of all 16 foods.Scores ranged from 5-15 (mean 10.7, SD 2.5). On average, respondents restricted 1-2 (mean1.4, SD 1.3, range 0-6) of 6 foods allowed, and consumed 0-1 (mean 0.4, SD 0.7; range0-2) of two foods not allowed. With respect to foods to question, respondents tended tobe overly restrictive by completely excluding an average of 3 of 8 foods in this category.Modified corn starch and glutinous rice were the GF foods most commonly restricted. Speltwas recognized as a gluten-containing grain by only 77% of respondents and 11% believedspelt is always GF. There was no association between self-reported "strict adherence" to aGFD and ability to correctly identify GF foods (p=0.82). Conclusions: Fewer patients withCD and/or DH self-reported strict adherence to a GFD when the possibility of unintentionalgluten ingestion was also included as an option. Patients following a GFD are not readilyable to correctly identify foodswhich are GF. These findings suggest ongoing gluten consump-tion is common, even among patients who believe they are "strict" dietary adherers. Furtherstudy is needed to determine whether this continued gluten consumption is the cause ofcontinuedmucosal damage in patients with celiac disease who are "strictly adherent" to a GFD.

Sa1269

Serum Anti-Gal Levels in Celiac Disease PatientsRohini R. Vanga, Alan Bonder, Ping Ping Kuang, Timothy M. Block, Daryl Lau, Ciaran P.Kelly, Anand Mehta, Daniel A. Leffler

Background - Anti-Galα-1-3Galβ1-(3)4GIcNAc-R (anti-α-Gal) is an immunoglobulin G pro-duced in response to immune stimulation by alpha-gal containing organisms, such as entericbacteria. A subset of these anti-alpha antibodies can be detected by their ability to reactwith the Aleuria Aurentia Lectin (AAL). Elevated titers of circulating AAL-reactive anti- α-Gal have been previously reported in crohn's disease and various autoimmune diseases suchas rheumatoid arthritis and systemic lupus. Celiac disease is an autoimmune conditiontriggered by gluten and closely associated with alterations in gut microbiome. We hypothe-sized that patients with active celiac disease would exhibit alterations in the circulating levelsof this AAL-reactive anti-α-Gal. Methods - Serum samples from active and treated adultswith celiac disease (CD) as well as healthy controls were collected. The demographic features,serum tissue transglutaminase (tTG) levels and histologic features were recorded. Serumanti-GAL levels were measured by a high-affinity ELISA, and converted to a fold change(FC) referenced to a standard control. Results - The sera of 45 subjects (15 active CD, 15treated CD and 15 healthy controls) were analyzed for anti- α-GAL levels. The mean age ofactive CD patients was 35.8 years (11 female; 4 male) and the median tTG level was 116units (range 62-120 units, normal , 20). The mean age of treated CD patients was 45.9years (11 female; 4 male) and the median tTG level was 8 units (range 2-16 units). Allpatients with CD had villous atrophy. The mean age of healthy controls was 38.5 years (10female; 5 male). The anti-α-GAL levels as measured by high-affinity ELISA were similar inall three groups with mean value of 1.7 in each group and the corresponding mean foldchange value was 4.9 in active (range 2.3 to 6.6) and treated (range 3.6 to 6.4) CD; 5.0 inhealthy controls (range 2.8 to 7.6). Conclusion - The normal gut microbiome is altered invarious gastrointestinal disorders. Our results show that the serum levels of lectin-reactiveanti-α-GAL are not altered in patients with celiac disease. Thus, the lack of correlation ofanti-α-GAL with celiac disease suggests that the alterations in intestinal permeability andthe composition of the gut microbiome may be different in celiac disease in comparison toother common autoimmune and inflammatory disorders.

Sa1270

Differential IL-13 and TNFα Production by Lamina Propria DerivedLeucocytes in Uncomplicated and Refractory Celiac DiseaseSascha Gross, Petula Nijeboer, Chris J. Mulder, Gerd Bouma, Boudewina M. vonBlomberg, Hetty Bontkes

Celiac disease (CD) is a gluten-sensitive autoimmune enteropathy with a prevalence of ca.one percent. A small fraction of CD patients, does not recover despite strict exclusion ofgluten from the diet. After exclusion of other enteropathies refractory celiac disease (RCD)is diagnosed in these patients. While in CD the immunopathology has been extensivelystudied, less is known in RCD where the inflammation is not gluten-driven. In order toexplore potential mediators of RCD we measured IL-5, IL-10, IL-13, IL-17, INF γ and TNFαin 28 consecutive CD and RCD patients. CD patients were divided into active CD (aCD),i.e. before start of the gluten-free diet and inactive CD (iCD), i.e. after having recoveredhistologically and serologically on the gluten-free diet. Analogously, RCD patients weredivided into active RCD (aRCD), i.e. with histological lesions and inactive RCD (iRCD), i.e.without histological lesions. The cytokines were measured from supernatant of 24h-culturedlamina propria CD45+ leucocytes stimulated with PMA and ionomycin. IL-13 productionwas significantly higher in aRCD patients as compared to aCD patients (p=0.004). HoweverIL-13 levels were also significantly increased in iCD patients on a gluten-free diet comparedto aCD patients (p=0.04), indicating that IL-13 producing cells may be reduced in thepresence of gluten. To a lesser extent this also holds true for TNF α, which is significantlyincreased in iCD patients on a gluten-free diet compared to aCD patients (p=0.02); in aRCDTNFα levels were also higher but the difference was not significant. For all the other cytokinesno differences between the groups were observed. These data indicate that IL-13 and TNF αprobably do not selectively contribute to the persisting villous atrophy in RCD patients.

AG

AA

bst

ract

s

AG

AA

bst

ract

s

Sa1271

A Clinical Predictive Model for Differentiation of Celiac Disease and Non-Celiac Gluten SensitivityToufic A. Kabbani, Rohini R. Vanga, Javier A. Villafuerte-Galvez, Kumar Pallav, RupaMukherjee, Melinda Dennis, Daniel A. Leffler, Ciaran P. Kelly

Background: Differentiating between Celiac Disease (CD) and Non-Celiac Gluten Sensitivity(NCGS) is important for appropriate management yet often challenging. Currently, there is alack of evidence based recommendations for evaluation of patients reporting gluten responsivesymptoms to identify those with CD versus NCGS. Methods: We retrospectively reviewedrecords from 238 patients who presented to our center for evaluation of symptoms responsiveto the gluten free diet (GFD). Demographics, presenting symptoms, serologic, genetic andhistologic data, nutrient deficiencies, personal history of autoimmune diseases and familyhistory of celiac disease were recorded. NCGS was defined as symptoms responsive to aGFD in the setting of negative serology and duodenal biopsies or in the setting of negativeHLA DQ2/DQ8 testing. Results: 52.5% and 42.4% of the cohort subjects had NCGS andCD respectively. Nine subjects (3.8%) had non-celiac enteropathy (NCE) and three (1.3%)had an indeterminate diagnosis (Figure 1). 76.2% and 78.4% of the CD and NCGS subjectswere female respectively (p=0.8). NCGS subjects had a significantly earlier age of onset ofsymptoms compared to CD subjects (38.0 years vs. 42.2 years, p=0.003). CD subjectspresented with typical malabsorptive symptoms 67.3% of the time compared to only 24.8%of the GS subjects (p,0.0001). Additionally, CD subjects were significantly more likely tohave family history of CD, personal history of auto-immune diseases or nutrient deficiencies(Table 1). The sensitivity and specificity of a .2x ULN tTG or DGP with clinical responseto GFD for CD were 97% (CI: 91.5%-99%) and 100% (CI: 97.3%-100%), respectively(Figure 1). Similarly, the sensitivity and specificity of the combination of gluten responsivesymptoms and negative tTG or DGP on a regular diet for NCGS were 93.6% (CI: 87.9%-96.7%) and 90.3% (CI: 83.4%-94.5%), respectively (Figure 1). When individuals withnegative tTG or DGP also lacked malabsorptive symptoms or signs (weight loss, diarrhea,and nutrient deficiencies) and CD risk factors (personal history of autoimmune diseases andfamily history of CD), the specificity for NCGS increased to 100% (Figure 2). Conclusions:We analyzed findings from patients presenting with gluten responsive symptoms to developa clinical algorithm for differentiation between CD and NCGS. Celiac serologies (tTG or

S-248AGA Abstracts

DGP) are an important first step. Those with positive serology are highly likely to have CD.Those with borderline serology can undergo HLA typing to determine the need for biopsy.Those with negative serology who also lack clinical evidence of malabsorption and CD riskfactors are highly likely to have NCGS and may not require biopsy.Clinical and demographic differences between CD and NCGS

*Nutrient deficiency is defined as vitamin D, iron, vitamin B12, or Zn deficiency.

Abbreviations: .2x ULN; more than twice the upper limit of normal, CD; Celiac Disease,NCGS; Non-Celiac Gluten Sensitivity, NCE; Non-Celiac Enteropathy

Sa1272

Myeloid Derived Suppressor Cell Frequencies Are Increased in ActiveRefractory Celiac DiseaseSascha Gross, Petula Nijeboer, Chris J. Mulder, Gerd Bouma, Boudewina M. vonBlomberg, Tanja D. de Gruijl, Hetty Bontkes

The gluten-driven Th1 response in celiac disease (CD) leads to enterocyte apoptosis andvillous atrophy. In most cases celiac disease is successfully treated with a gluten-free diet.However, a small proportion of patients becomes non-responsive and enteropathy persistsdespite a strict adherence to a gluten-free diet, i.e. refractory celiac disease (RCD). Thus,whereas in untreated active celiac disease the immune response against enterocytes is gluten-driven, this is not the case in RCD. We hypothesised that the immune responses in thesedisease states may be differentially regulated by suppressive cells. We therefore analysedgranulocytic CD15+CD11b+CD33+ and monocytic CD14+HLA-DR- myeloid-derived sup-pressor cells (MDSC) in single cell suspensions of the lamina propria and in the peripheralblood of celiac disease patients. In addition, cytokine production after polyclonal activationof lamina propria CD45+ leucocytes was assessed. The following groups were defined: activeceliac disease patients (ACD) with villous atrophy (Marsh 3); patients on a gluten free diet(GFD) without celiac disease associated antibodies and without villous atrophy (Marsh 0-2) and RCD patients not responding to therapy with persisting villous atrophy. MonocyticMDSC were present at low frequencies in all groups. Granulocytic MDSC were significantlyincreased in the lamina propria of RCD patients but not in the peripheral blood. Productionof TNFα and IL-13, cytokines associated with a chronic inflammatory state in the bowel,was significantly higher in RCD as compared to ACD. The high frequency of MDSC in activeRCD together with elevated levels of inflammatory cytokines is consistent with a chronicinflammatory state with resistance to immune regulation. This differential immune regulationbetween untreated active and refractory celiac disease may provide clues as to effectivetreatment approaches.

Sa1273

Increased Prevalence of Celiac Specific Antibody in Japanese IBD Patients andthe Effect of Gluten IntakeChikako Watanabe, Shunsuke Komoto, Chie Kurihara, Yoshikiyo Okada, KazuyukiNarimatsu, Hirokazu Sato, Hideaki Hozumi, Ryota Hokari, Soichiro Miura

Objectives: The incidence of celiac disease has been increasing in Western and parts ofAsian countries. Wheat consumption has increased in Japan over the past decades, but theprevalence of celiac disease remains unknown. The aim of this study was to investigate theprevalence of celiac disease and celiac disease-specific antibodies in Japan where the geneticdisposition is presumed to be low. Especially we focused on the positivity of the antibodiesin relation to clinical characteristics of inflammatory bowel disease (IBD) patients, becausethe high prevalence of celiac disease-specific antibodies has been reported in IBD, and itsclinical significance is contentious without villous atrophy. Furthermore, we followed upsome sero-positive IBD patients with or without gluten for three years to investigate theeffect of gluten intake. Methods: A total of 172 patients with IBD (110 ulcerative colitisand 62 Crohn's disease) and 190 controls were prospectively enrolled. Diagnosis of IBDwas based on the standard criteria. All participants were screened for celiac specific antibodies,tissue transglutaminase (tTG) and deaminated gliadine peptide (DGP). In sero-positivepatients, anti-endomysial antibody, HLA typing and esophagogastroduodenoscopy with duo-denal biopsy were performed. Sero-positive patients were randomized to a gluten-restrictedor unrestricted diet, and clinical symptoms, antibody titers and duodenal biopsy werefollowed every 6-12 months. Results: The prevalence of tTG was 19.4%, 9.1% and 1.6%