Gluten immunogenic peptide excretion detects dietary transgressions in treated celiac disease patients.

BACKGROUND: Life-long removal of gluten from the diet is currently the only way to manage celiac disease (CeD). Until now, no objective test has proven useful to objectively detect ingested gluten in clinical practice. Recently, tests that determine consumption of gluten by assessing excretion of gluten immunogenic peptides (GIP) in stool and urine have been developed. Their utility, in comparison with conventional dietary and analytical follow-up strategies, has not been fully established. AIM: To assess the performance of enzyme-linked immunosorbent assay (ELISA) and point-of-care tests (PoCTs) for GIP excretion in CeD patients on gluten-free diet (GFD). METHODS: We conducted an observational, prospective, cross-sectional study in patients following a GFD for at least two years. Using the Gastrointestinal Symptom Rating Scale questionnaire, patients were classified at enrollment as asymptomatic or symptomatic. Gluten consumption was assessed twice by 3-d dietary recall and GIP excretion (by ELISA in stool and PoCTs (commercial kits for stool and urine) in two consecutive samples. These samples and dietary reports were obtained 10 day apart one from the other. Patients were encouraged to follow their usual GFD during the study period. RESULTS: Forty-four patients were enrolled, of which 19 (43.2%) were symptomatic despite being on a GFD. Overall, 83 sets of stool and/or urine samples were collected. Eleven out of 44 patients (25.0%) had at least one positive GIP test. The occurrence of at least one positive test was 32% in asymptomatic patients compared with 15.8% in symptomatic patients. GIP was concordant with dietary reports in 65.9% of cases (Cohen´s kappa: 0.317). PoCT detected dietary indiscretions. Both ELISA and PoCT in stool were concordant (concomitantly positive or negative) in 67 out of 74 (90.5%) samples. Excretion of GIP was detected in 7 (8.4%) stool and/or urine samples from patients considered to be strictly compliant with the GFD by dietary reports. CONCLUSION: GIP detects dietary transgressions in patients on long-term GFD, irrespective of the presence of symptoms. PoCT for GIP detection constitutes a simple home-based method for self-assessment of dietary indiscretions.

Impaired Bone Microarchitecture Improves After One Year On Gluten-Free Diet: A Prospective Longitudinal HRpQCT Study in Women With Celiac Disease.

We have recently identified a significant deterioration of bone microarchitecture in premenopausal women with newly diagnosed celiac disease (CD) using high-resolution peripheral quantitative computed tomography (HRpQCT). The aim of this work was to assess changes in bone microarchitecture after 1 year on a gluten-free diet (GFD) in a cohort of premenopausal women. We prospectively enrolled 31 consecutive females at diagnosis of CD; 26 of them were reassessed 1 year after GFD. They all underwent HRpQCT scans of distal radius and tibia, areal BMD by DXA, and biochemical tests (bone-specific parameters and CD serology) at both time points. Secondary, we compared 1-year results with those of a control group of healthy premenopausal women of similar age and BMI in order to assess whether the microarchitectural parameters of treated CD patients had reached the values expected for their age. Compared with baseline, the trabecular compartment in the distal radius and tibia improved significantly (trabecular density, trabecular/bone volume fraction [BV/TV] [p < 0.0001], and trabecular thickness [p = 0.0004]). Trabecular number remained stable in both regions. Cortical density increased only in the tibia (p = 0.0004). Cortical thickness decreased significantly in both sites (radius: p = 0.03; tibia: p = 0.05). DXA increased in all regions (lumbar spine [LS], p = 0.01; femoral neck [FN], p = 0.009; ultradistal [UD] radius, p = 0.001). Most parameters continued to be significantly lower than those of healthy controls. This prospective HRpQCT study showed that most trabecular parameters altered at CD diagnosis improved significantly by specific treatment (GFD) and calcium and vitamin D supplementation. However, there were still significant differences with a control group of women of similar age and BMI. In the prospective follow-up of this group of patients we expect to be able to assess whether bone microarchitecture attains levels expected for their age. © 2016 American Society for Bone and Mineral Research.

Bifidobacterium infantis NLS Super Strain Reduces the Expression of α-Defensin-5, a Marker of Innate Immunity, in the Mucosa of Active Celiac Disease Patients.

BACKGROUND: We have previously shown a reduction of gastrointestinal symptoms after the oral administration of Bifidobacterium infantis Natren Life Start super strain (NLS-SS) in untreated celiac disease (CD) patients. The symptomatic improvement was not associated with changes in intestinal permeability or serum levels of cytokines, chemokines, or growth factors. Therefore, we hypothesized that the beneficial symptomatic effect observed previously in patients with CD treated with B. infantis may be related to the modulation of innate immunity. GOALS: To investigate the potential mechanisms of a probiotic B. infantis Natren Life Start super strain on the mucosal expression of innate immune markers in adult patients with active untreated CD compared with those treated with B. infantis×6 weeks and after 1 year of gluten-free diet (GFD). METHODS: Numbers of macrophages and Paneth cells and α-defensin-5 expression were assessed by immunohistochemistry in duodenal biopsies. RESULTS: We showed that GFD decreases duodenal macrophage counts in CD patients more effectively than B. infantis. In contrast, B. infantis decreases Paneth cell counts and expression of α-defensin-5 in CD (P<0.001). CONCLUSIONS: The results identify differential innate immune effects of treatment with B. infantis compared with 1 year of GFD. Further studies are needed to investigate synergistic effects of GFD and B. infantis supplementation in CD.

Prevalence of celiac disease and celiac autoimmunity in the Toba Native Amerindian community of Argentina.

BACKGROUND: Celiac disease (CD) is mostly recognized among subjects with a Caucasian ethnic ancestry. No studies have explored conditions predisposing Amerindians to CD. OBJECTIVE: To prospectively assess environmental, genetic and serological conditions associated with CD among members of the Toba native population attending a multidisciplinary sanitary mission. METHODS: An expert nutritionist determined daily gluten intake using an established questionnaire. Gene typing for the human leukocyte antigen (HLA) class II alleles was performed on DNA extracted from peripheral blood (HLA DQ2/DQ8 haplotype). Serum antibodies were immunoglobulin (Ig) A tissue transglutaminase (tTG) and the composite deamidated gliadin peptides/tTG Screen test. Positive cases were tested for IgA endomysial antibodies. RESULTS: A total of 144 subjects (55% female) were screened. The estimated mean gluten consumption was 43 g/day (range 3 g/day to 185 g/day). Genetic typing showed that 73 of 144 (50.7%) subjects had alleles associated with CD; 69 (94.5%) of these subjects had alleles for HLA DQ8 and four had DQ2 (5.5%). Four and six subjects had antibody concentrations above the cut-off established by the authors' laboratory (>3 times the upper limit of normal) for IgA tTG and deamidated gliadin peptides/tTG screen, respectively. Four of these had concomitant positivity for both assays and endomysial antibodies were positive in three subjects who also presented a predisposing haplotype. CONCLUSION: The present study was the first to detect CD in Amerindians. The native Toba ethnic population has very high daily gluten consumption and a predisposing genetic background. We detected subjects with persistent CD autoimmunity and, at least, three of them fulfilled serological criteria for CD diagnosis.

Exploratory, randomized, double-blind, placebo-controlled study on the effects of Bifidobacterium infantis natren life start strain super strain in active celiac disease.

BACKGROUND/AIMS: The aim of this exploratory trial was to establish if the probiotic Bifidobacterium natren life start (NLS) strain strain may affect the clinical course and pathophysiological features of patients with untreated celiac disease (CD). Positive findings would be helpful in directing future studies. METHODS: Twenty-two adult patients having 2 positives CD-specific tests were enrolled. Patients were randomized to receive 2 capsules before meals for 3 weeks of either Bifidobacterium infantis natren life start strain super strain (Lifestart 2) (2×10(9) colony-forming units per capsule) (n = 12) or placebo (n = 10), whereas they also consumed at least 12 g of gluten/day. A biopsy at the end of the trial confirmed CD in all cases. The primary outcome was intestinal permeability changes. Secondary endpoints were changes in symptoms and the Gastrointestinal Symptom Rating Scale, and in immunologic indicators of inflammation. RESULTS: The abnormal baseline intestinal permeability was not significantly affected by either treatment. In contrast to patients on placebo, those randomized to B. infantis experienced a significant improvement in Gastrointestinal Symptom Rating Scale (P = 0.0035 for indigestion; P = 0.0483 for constipation; P = 0.0586 for reflux). Final/baseline IgA tTG and IgA DGP antibody concentration ratios were lower in the B. infantis arm (P = 0.055 for IgA tTG and P = 0.181 for IgA DGP). Final serum macrophage inflammatory protein-1ß increased significantly (P < 0.04) only in patients receiving B. infantis. The administration of B. infantis was safe. CONCLUSIONS: The study suggests that B. infantis may alleviate symptoms in untreated CD. The probiotic produced some immunologic changes but did not modify abnormal intestinal permeability. Further studies are necessary to confirm and/or expand these observations.

Estudio epidemiológico prospectivo para el análisis de la prevalencia de enfermedad celíaca en pacientes con constipación crónica / Prospective epidemiological study for the analysis of prevalence of celiac disease in patients with chronic constipation

INTRODUCCION: Aunque la enfermedad celíaca (EC) se asocia comúnmente a diarrea crónica, 10% de los casos pueden presentarse con constipación crónica (CC). No hay estudios que exploren la prevalencia de EC o marcadores potenciales de la sensibilidad al gluten (SG) en pacientes que consultan por CC.OBJETIVO: Determinar la prevalencia de marcadores potenciales de SG y EC en pacientes con CC que consultan a un centro terciario de referencia.METODOS: Estudio exploratorio prospectivo. Se evaluó a 121 pacientes adultos consecutivos con diagnóstico de CC funcional (67,8%) o SII-C (criterios de Roma III) con anticuerpos contra péptidos deamidados de gliadina IgA e IgG y anti-transglutaminasa tisular (DGP/tTGscreen valor corte=20). Los casos seropositivos fueron analizados con IgA tTG y todos los DGP/tTG Screen casos positivos se sometieron a biopsias endoscópicas de duodeno. La prevalencia se comparó con la de 518 sujetos (endoscopía digestiva alta por síntomas no relacionados primariamente con EC) y con la estimada para la población urbana del Gran La Plata. Se consideró diagnóstico de EC a la presencia de una enteropatía Marsh Illa o mayor en los casos seropositivos. Se consideró SG a los casos seropositivos sin enteropatía ni autoanticuerpos (IgA tTG).RESULTADOS: 10 pacientes (8,3%) y 46 sujetos del grupo control (8,9%) con CC tuvieron resultados positivos DGP/tTG Screen. 3 pacientes seropositivos con CC y 14 controles presentaron biopsia compatible con EC. Se estimó una prevalencia de 2,5% para los pacientes con CC y 2,7% para los controles. La prueba de IgA tTG fue positiva en 5 de los 10 pacientes con CC (incluidos los 2 casos diagnosticados con EC) y en 13 controles (100% y 92% de sensibilidad, respectivamente), 5 pacientes con CC fueron considerados como SG.CONCLUSIONES: Este estudio fue el primero en determinar la prevalencia en EC y SG en pacientes con CC, la cual resultó casi cuatro veces mayor que la estimada para la población general de Argentina (1/133).

INTRODUCTION: Celiac disease (CD) diagnosis is strongly associated with the presence of chronic diarrhea, but up to 10% of newly diagnosed cases may complain of chronic constipation (CC). No studies have explored the prevalence of CD or potential markers of gluten sensitivity among patients consulting for CC.OBJECTIVE: TO determine the prevalence of potential markers of gluten sensitivity and CD in a series of consecutive patients with chronic constipation attending a tertiary referral center.METHODS: An exploratory study was conducted at Gastroenterology Hospital of Buenos Aires. 121 adult consecutive patients with diagnosis of chronic constipation (67.8%) or IBS-C (Rome III criteria) were assessed for antibodies to deamidatedgliadin peptides IgA and IgG and tissue transglutaminase (DGP/tTG Screen cut-off: 20 U/mL). Seropositive cases were tested (IgA tTG) and all DGP/tTG Screen positive cases underwent duodenal biopsies. Prevalece was compared with that obtained from a control population of 518 subjects (upper endoscopy due to symptoms not primarily related to CD). Type Illa Marsh’s enteropathy or greater in seropositive cases was considered as CD diagnosis.RESULTS: 10 patients (8.3%) and 46 controls (8.9%) with CC had a positive DGP/tTGScreen test. 3 seropositive patients with CC and 14 controls had a CD compatible biopsy. The IgA tTG test was positive in 5 of the 10 patients with CC (including those 3 cases finally diagnosed with CD) and in 13 from control population (100% and 92% sensitivity, respectively). 5 patients with CC were considered as gluten sensitive (serology positive, but no enteropathy).CONCLUSIONS: This study was the first to determine a higher prevalence of CD and gluten sensitivity in patients complaining of CC. This prevalence was almost four times greater than that estimated for the general Argentinean population (1/133).

Estudio epidemiológico prospectivo para el análisis de la prevalencia de enfermedad celíaca en pacientes con constipación crónica / Prospective epidemiological study for the analysis of prevalence of celiac disease in patients with chronic constipation

INTRODUCCION: Aunque la enfermedad celíaca (EC) se asocia comúnmente a diarrea crónica, 10% de los casos pueden presentarse con constipación crónica (CC). No hay estudios que exploren la prevalencia de EC o marcadores potenciales de la sensibilidad al gluten (SG) en pacientes que consultan por CC.OBJETIVO: Determinar la prevalencia de marcadores potenciales de SG y EC en pacientes con CC que consultan a un centro terciario de referencia.METODOS: Estudio exploratorio prospectivo. Se evaluó a 121 pacientes adultos consecutivos con diagnóstico de CC funcional (67,8%) o SII-C (criterios de Roma III) con anticuerpos contra péptidos deamidados de gliadina IgA e IgG y anti-transglutaminasa tisular (DGP/tTGscreen valor corte=20). Los casos seropositivos fueron analizados con IgA tTG y todos los DGP/tTG Screen casos positivos se sometieron a biopsias endoscópicas de duodeno. La prevalencia se comparó con la de 518 sujetos (endoscopía digestiva alta por síntomas no relacionados primariamente con EC) y con la estimada para la población urbana del Gran La Plata. Se consideró diagnóstico de EC a la presencia de una enteropatía Marsh Illa o mayor en los casos seropositivos. Se consideró SG a los casos seropositivos sin enteropatía ni autoanticuerpos (IgA tTG).RESULTADOS: 10 pacientes (8,3%) y 46 sujetos del grupo control (8,9%) con CC tuvieron resultados positivos DGP/tTG Screen. 3 pacientes seropositivos con CC y 14 controles presentaron biopsia compatible con EC. Se estimó una prevalencia de 2,5% para los pacientes con CC y 2,7% para los controles. La prueba de IgA tTG fue positiva en 5 de los 10 pacientes con CC (incluidos los 2 casos diagnosticados con EC) y en 13 controles (100% y 92% de sensibilidad, respectivamente), 5 pacientes con CC fueron considerados como SG.CONCLUSIONES: Este estudio fue el primero en determinar la prevalencia en EC y SG en pacientes con CC, la cual resultó casi cuatro veces mayor que la estimada para la población general de Argentina (1/133).

INTRODUCTION: Celiac disease (CD) diagnosis is strongly associated with the presence of chronic diarrhea, but up to 10% of newly diagnosed cases may complain of chronic constipation (CC). No studies have explored the prevalence of CD or potential markers of gluten sensitivity among patients consulting for CC.OBJECTIVE: TO determine the prevalence of potential markers of gluten sensitivity and CD in a series of consecutive patients with chronic constipation attending a tertiary referral center.METHODS: An exploratory study was conducted at Gastroenterology Hospital of Buenos Aires. 121 adult consecutive patients with diagnosis of chronic constipation (67.8%) or IBS-C (Rome III criteria) were assessed for antibodies to deamidatedgliadin peptides IgA and IgG and tissue transglutaminase (DGP/tTG Screen cut-off: 20 U/mL). Seropositive cases were tested (IgA tTG) and all DGP/tTG Screen positive cases underwent duodenal biopsies. Prevalece was compared with that obtained from a control population of 518 subjects (upper endoscopy due to symptoms not primarily related to CD). Type Illa Marshs enteropathy or greater in seropositive cases was considered as CD diagnosis.RESULTS: 10 patients (8.3%) and 46 controls (8.9%) with CC had a positive DGP/tTGScreen test. 3 seropositive patients with CC and 14 controls had a CD compatible biopsy. The IgA tTG test was positive in 5 of the 10 patients with CC (including those 3 cases finally diagnosed with CD) and in 13 from control population (100% and 92% sensitivity, respectively). 5 patients with CC were considered as gluten sensitive (serology positive, but no enteropathy).CONCLUSIONS: This study was the first to determine a higher prevalence of CD and gluten sensitivity in patients complaining of CC. This prevalence was almost four times greater than that estimated for the general Argentinean population (1/133).

Serological tests for celiac disease as indicators of long-term compliance with the gluten-free diet.

OBJECTIVES: The efficacy of celiac disease (CD)-related antibodies in monitoring clinical outcome of patients remains unclear. Our aims were to determine dynamics of antibodies after diagnosis and to assess their performances in monitoring patients' long-term compliance with the gluten-free diet (GFD). METHODS: We prospectively estimated the performance of seven celiac disease-related antibody tests at diagnosis and at 1 year and more than 4 years after treatment initiation in 53 adults. The ability of antibodies to identify patients partially compliant to treatment was explored by the receiver operating characteristic curve analysis. The derived cut-off values ('compliance' cutoffs) were compared with cut-off values used for diagnosis ('diagnostic' cutoffs). The degree of compliance with the GFD was assessed using a standardized, multidisciplinary approach. RESULTS: Concentrations of all antibodies decreased significantly at 1 year after diagnosis. The decline continued for more than 4 years in strictly compliant patients (P<0.05-0.001). The gap between 'compliance' and 'diagnostic' cut-offs values was wider at 1 year than at more than 4 years. The predictability of partial compliance determined by the area under receiver operating characteristic curves was relevant for most tests examined at 1 year (areas ranging: 0.64-0.72) and more than 4 years (0.58-0.78). Immunoglobulin A antibodies to deamidated gliadin peptides and tissue transglutaminase had the best performance for monitoring long-term compliance. CONCLUSION: Decreased concentrations of antibodies were significantly associated with the degree of compliance with the GFD. Immunoglobulin A antibodies to deamidated gliadin peptides and tissue transglutaminase had the best and more consistent performances. The serial measurement of antibody levels seems to be more reliable in monitoring compliance than the positive/negative expression of results.

Gastroesophageal reflux symptoms in patients with celiac disease and the effects of a gluten-free diet.

BACKGROUND & AIMS: Celiac disease (CD) patients often complain of symptoms consistent with gastroesophageal reflux disease (GERD). We aimed to assess the prevalence of GERD symptoms at diagnosis and to determine the impact of the gluten-free diet (GFD). METHODS: We evaluated 133 adult CD patients at diagnosis and 70 healthy controls. Fifty-three patients completed questionnaires every 3 months during the first year and more than 4 years after diagnosis. GERD symptoms were evaluated using a subdimension of the Gastrointestinal Symptoms Rating Scale for heartburn and regurgitation domains. RESULTS: At diagnosis, celiac patients had a significantly higher reflux symptom mean score than healthy controls (P < .001). At baseline, 30.1% of CD patients had moderate to severe GERD (score >3) compared with 5.7% of controls (P < .01). Moderate to severe symptoms were significantly associated with the classical clinical presentation of CD (35.0%) compared with atypical/silent cases (15.2%; P < .03). A rapid improvement was evidenced at 3 months after initial treatment with a GFD (P < .0001) with reflux scores comparable to healthy controls from this time point onward. CONCLUSIONS: GERD symptoms are common in classically symptomatic untreated CD patients. The GFD is associated with a rapid and persistent improvement in reflux symptoms that resembles the healthy population.

Celiac disease serology in patients with different pretest probabilities: is biopsy avoidable?

AIM: To establish the diagnostic performance of several serological tests, individually and in combination, for diagnosing celiac disease (CD) in patients with different pretest probabilities, and to explore potential serological algorithms to reduce the necessity for biopsy. METHODS: We prospectively performed duodenal biopsy and serology in 679 adults who had either high risk (n = 161) or low risk (n = 518) for CD. Blood samples were tested using six assays (enzyme-linked immunosorbent assay) that detected antibodies to tissue transglutaminase (tTG) and deamidated gliadin peptide (DGP). RESULTS: CD prevalence was 39.1% in the high-risk population and 3.3% in the low-risk group. In high-risk patients, all individual assays had a high diagnostic efficacy [area under receiving operator characteristic curves (AU ROC): 0.968 to 0.999]. In contrast, assays had a lower diagnostic efficacy (AU ROC: 0.835 to 0.972) in the low-risk group. Using assay combinations, it would be possible to reach or rule out diagnosis of CD without biopsy in 92% of cases in both pretest populations. We observed that the new DGP/tTG Screen assay resulted in a surplus compared to more conventional assays in any clinical situation. CONCLUSION: The DGP/tTG Screen assay could be considered as the best initial test for CD. Combinations of two tests, including a DGP/tTG Screen, might be able to diagnose CD accurately in different clinical scenarios making biopsy avoidable in a high proportion of subjects.

Long-term deterioration of quality of life in adult patients with celiac disease is associated with treatment noncompliance.

BACKGROUND: Deterioration of quality of life in the long term has been suggested for celiac disease patients on a gluten-free diet. AIMS: To determine long-term quality of life of celiac disease patients and to assess the benefits of gluten-free diet compliance. PATIENTS: We prospectively evaluated 53 newly diagnosed adult celiac disease patients. METHODS: The Short Form 36 Health Survey, the Gastrointestinal Symptoms Rating Scale and the Beck Depression Inventory were employed at the time of diagnosis, 1 year, and beyond 4 years (median: 53 months) on treatment. RESULTS: At 1 year, a significant improvement from baseline in quality of life indicators was observed (p<0.001 to p<0.0001) with comparable scores to healthy subjects. At 4 years, the Short Form 36 Health Survey scores (p<0.002 to p<0.0002) and Beck Depression Inventory score (p<0.002) show significant deterioration compare with 1 year. Most scores remained significantly better than those at diagnosis (p<0.03 to p<0.0005). No changes were detected in the Gastrointestinal Symptoms Rating Scale scores. The long-term impairment of quality of life was attributable to the deterioration of most dimensions in patients who were not strictly compliant with the gluten-free diet (p<0.05 to p<0.001). CONCLUSIONS: Long-term deterioration of quality of life outcomes after the first year of gluten-free diet was associated with the lack of strict compliance with the diet.

New serology assays can detect gluten sensitivity among enteropathy patients seronegative for anti-tissue transglutaminase.

BACKGROUND: Some patients with celiac disease (CD) may be seronegative with the commonly used test for IgA anti-tissue transglutaminase (anti-tTG) antibodies. Our aim was to explore whether newer assays incorporating synthetic deamidated gliadin-related peptides (DGPs) or other TG isoenzymes as antigen are useful for detecting gluten sensitivity in IgA anti-tTG-seronegative patients. METHODS: We assayed serum samples obtained at diagnosis from (a) anti-tTG-seronegative patients with a CD-like enteropathy (n = 12), (b) skin biopsy-proven dermatitis herpetiformis (DH) patients (n = 26), and (c) IgA anti-tTG-positive CD patients (n = 26). All patients had typical total IgA concentrations. All patients underwent intestinal biopsy and serum testing for (a) detection of IgA and IgG isotypes of both anti-DGP and anti-tTG in a single assay (tTG/DGP Screen; INOVA Diagnostics), (b) simultaneous detection of both IgA and IgG anti-DGP antibody isotypes (DGP Dual; INOVA Diagnostics), and (c) detection of antibodies to transglutaminase 3 (TG3) or transglutaminase 6 (TG6). RESULTS: All anti-tTG-seropositive patients also tested positive in anti-DGP assays. Overall, tTG/DGP Screen detected 6 (31.6%) of the 19 anti-tTG seronegatives, and anti-DGP Dual produced positive results in 5 (26.3%) of these cases. Whereas both assays detected 2 anti-tTG-negative DH patients with partial villous atrophy, they were positive in only 2 of the 5 cases with no histologically discernible mucosal damage. Testing for antibodies to TG3 and TG6 identified 7 (36.8%) of the 19 anti-tTG-negative patients, 5 of which were also positive for anti-DGP. CONCLUSIONS: Detection of anti-DGP with tTG/DGP Screen or anti-DGP Dual, or detection of antibodies to other TG isoenzymes, enhances the sensitivity for detecting gluten sensitivity among non-IgA- deficient, anti-tTG-seronegative patients with CD-like enteropathy.

Dynamics of celiac disease-specific serology after initiation of a gluten-free diet and use in the assessment of compliance with treatment.

BACKGROUND: The usefulness of celiac disease-related serology in monitoring patients on a gluten-free diet has been debated. AIM: To describe serologic changes over time and assess whether serology tests can predict compliance with the gluten-free diet. METHODS: Sera obtained at baseline and every 3 months thereafter for 1 year in 82 adult celiac disease patients were assayed for: (1) IgA antigliadin, (2) IgA anti-tissue transglutaminase, (3) IgA endomysial, (4) IgA, and (5) IgG anti-deamidated gliadin peptides, (6) dual detection of IgA and IgG anti-deamidated gliadin peptides, (7) a single assay for IgA and IgG of both anti-deamidated gliadin peptide and anti-tissue transglutaminase, and (8) IgA antiactin antibodies. RESULTS: At 3 months after diagnosis, most antibody assays significant decrease in mean concentrations (p<0.0001) and the percentage of positive samples (p<0.0001) with further improvement in subsequent determinations. Strictly adherents had significantly lower concentrations of antibodies (p<0.01 to p<0.00001) and smaller proportion of positive samples for IgA endomysial, IgA antiactin antibodies and IgA antigliadin (15.6%, 17.4% and 23.9%, respectively) than partially compliant. At 1 year, IgA endomysial (p<0.02), IgA antiactin antibodies (p<0.05) and anti-tissue transglutaminase (p<0.02) predicted the degree of compliance. CONCLUSIONS: Gluten-free diet treatment produced rapid and significant qualitative and quantitative changes in celiac disease-related antibodies which may be useful for monitoring dietary compliance.

Low-dose aspirin affects the small bowel mucosa: results of a pilot study with a multidimensional assessment.

BACKGROUND & AIMS: Whether low-dose aspirin (acetylsalicylic acid [ASA]) produces intestinal damage is controversial. Our aim was to determine whether the small bowel is damaged by low-dose ASA on a short-term basis. METHODS: Twenty healthy volunteers (age range, 19-64 years) underwent video capsule endoscopy (VCE), fecal calprotectin, and permeability tests (sucrose and lactulose/mannitol [lac/man] ratio) before and after ingestion of 100 mg of enteric-coated ASA daily for 14 days. Video capsule images were assessed by 2 independent expert endoscopists, fully blinded to the treatment group, by using an endoscopic scale. RESULTS: Post-ASA VCE detected 10 cases (50%) with mucosal damage not apparent in baseline studies (6 cases had petechiae, 3 had erosions, and 1 had bleeding stigmata in 2 ulcers). The median baseline lac/man ratio (0.021; range, 0.011-0.045) increased after ASA use (0.036; range, 0.007-0.258; P = .08), and the post-ASA lac/man ratio was above the upper end of normal (>0.025) in 10 of 20 volunteers (vs baseline, P < .02). The median baseline fecal calprotectin concentration (6.05 microg/g; range, 1.9-79.2) also increased significantly after ASA use (23.9 microg/g; range, 3.1-75.3; P < .0005), with 3 patients having values above the cutoff (>50 microg/g). Five of 10 subjects with abnormal findings at VCE also had lac/man ratios above the cutoff. Median baseline sucrose urinary excretion (70.0 mg; range, 11.8-151.3) increased significantly after ASA administration (107.0 mg; range, 22.9-411.3; P < .05). CONCLUSIONS: The short-term administration of low-dose ASA is associated with mucosal abnormalities of the small bowel mucosa, which might have implications in clinical practice.

A prospective evaluation of endoscopic markers for identifying celiac disease in patients with high and low probability of having the disease.

BACKGROUND/OBJECTIVES: the usefulness of duodenoscopic markers for predicting celiac disease (CD) has been questioned. We assessed the diagnostic efficacy of endoscopic markers of mucosal atrophy in individuals with different pretest probability of CD. METHODS: we prospectively performed endoscopic intestinal biopsies and CD-related serology tests in 661 individuals, including 143 consecutive patients attending a malabsorption clinic (high pretest probability) and 518 subjects randomly selected fom those undergoing routine endoscopy because of upper GI symptoms (low pretest probability). Duodenoscopic markers reported were: mosaic pattern, scalloped folds, and reduction in number or loss of Kerkring's folds. RESULTS: sixty-three (44.1%) and 18 (3.5%) patients were diagnosed with CD in the high and low risk groups, respectively Among high pretest subjects, the presence of any marker had very high sensitivity, specificity, positive predictive value, negative predictive value, and diagnostic accuracy for the identification of CD (92.1%, 93.8%, 92.1%, 93.8% and 93.0%, respectively). The performance of these parameters for the presence of any marker in the low pretest population were 61.1%, 96.8%, 40.7%, 98.6% and 95.6%, respectively. Sensitivity (p < 0.004) and positive predictive value (p < 0.0001) of markers were significantly higher for the high risk patients. The identification of a reduction in number or loss of Kerkring'sfolds was not a reliable finding unless other signs were also present. CONCLUSIONS: we confirm that endoscopic markers are useful in predicting CD in different clinical scenarios. The high negative predictive value in the low probability group suggests that intestinal biopsy is not required if endoscopic markers are absent.

Antibodies against synthetic deamidated gliadin peptides as predictors of celiac disease: prospective assessment in an adult population with a high pretest probability of disease.

BACKGROUND: Noninvasive serologic tests have shown high diagnostic accuracy for celiac disease (CD) in selected populations. Our aim was to determine prospectively the performance of CD-related serology in individuals undergoing intestinal biopsy because of clinical suspicion of small-bowel disorders. METHODS: We enrolled 141 unselected consecutive adult patients attending a small-bowel disease clinic. Patients underwent endoscopy and biopsy; serum samples were obtained at that time for measurements of anti-tissue transglutaminase (a-tTG), IgA and IgG anti-deamidated gliadin-related peptide (a-DGP), and IgA antiactin antibodies (AAAs). Characterization of patients was based on histological criteria (Marsh type II lesion or greater). RESULTS: The prevalence of CD was 42.5%. Sensitivity, specificity, and positive and negative predictive values were >90% for most assays. Diagnostic accuracy based on ROC curve analysis was similar for all assays [area under the curve (95% CI): 0.996 (0.967-0.998) for a-tTG, 0.995 (0.964-0.998) for IgA a-DGP, 0.989 (0.954-0.999) for IgG a-DGP, 0.996 (0.966-0.998) for blended conjugated of IgA + IgG a-DGP in a single assay, and 0.967 (0.922-0.990) for AAA]. The combinations of 2 tests, IgG a-DGP plus IgA a-tTG or the single blended conjugate detecting IgA + IgG a-DGP plus IgA a-tTG had 100% positive and negative predictive values if concentrations of both tests in either combination were above or below the cutoff. CONCLUSIONS: In a population with high pretest probability, the newly developed a-DGP tests have diagnostic accuracy that is at least equivalent to that of established assays.

Celiac disease serology in dermatitis herpetiformis: which is the best option for detecting gluten sensitivity? / Serología de enfermedad celíaca en dermatitis herpetiforme. ¿Cuál es la mejor opción para detectar sensibilidad al gluten?

Background: Dermatitis herpetiformis (DH), a wellestablished gluten-sensitive skin disorder presenting variable degrees of enteropathy, constitutes a very useful model in order to assess the utility of the celiac disease (CD)-related serology in patients with mild intestinal damage. Objective: Our aim was to explore comparatively the performance of a panel of CD-related serologic tests in patients with DH. Methods: We assessed a series of 18 consecutive patients with skin biopsy proven DH presenting the overall spectrum of intestinal damage ranging from normal mucosa (n=6) to total villous atrophy (TVA) (n=6) through partial villous atrophy (PVA) (n=6). Sera were obtained from all patients while consuming a gluten containing diet. Serologic tests were antiendomysial, anti-tissue transglutaminase and antigliadin antibodies, and newly developed tests detecting both antibody isotypes (IgA and IgG) against deamidated synthetic gliadin-derivedpeptides (a-GDP). Results: Serologic tests had a variable behaviour depending on the degree of enteropathy. While the majority of tests detected patients with TVA, only 50% of those with normal histology had positive assays. Patients with PVA had discordant results. Classical CD-specific tests were positive in only some patients with mild damage while all of them were identified by a single assay detecting both isotypes of a-GDP. Conclusion: The detection of a-GDP antibodies was the most reliable tool in order to identify gluten sensitivity in DH patients presenting a wide range of intestinal damage. Further studies should explore if these findings can be extrapolated to patients with CDhaving mild enteropathy.

Introducción: la dermatitis herpetiformis (DH), una lesión dermatológica consecuencia de sensibilidad al gluten y asociada a grados variables de enteropatía, constituye un modelo muy útil con el objeto de evaluar la eficacia de la serología de la enfermedad celíaca(EC) en pacientes con daño intestinal leve. Objetivo: explorar comparativamente la utilidad de una serie de anticuerpos empleados en EC en pacientes con DH. Métodos: analizamos una serie de 18 pacientes consecutivos con diagnóstico de DH por biopsia de piel que presentaban el más amplio espectro de daño intestinal variando desde una mucosa normal (n=6) a la atrofia vellosa total (AVT) (n=6) y pasando por atrofia vellosaparcial (AVP) (n=6). Se obtuvo plasma de todos los pacientes mientras consumían gluten. Las pruebas serológicas empleadas fueron anticuerpos antiendomisio, anti-transglutaminasa y atigliadina, y unas pruebas recientemente desarrolladas que detectan anticuerpos IgA e IgG dirigidos contra péptidos sintéticos deamidados derivados de la gliadina (a-GDP). Resultados: las diferentes pruebas tuvieron un comportamiento variable dependiendo del grado de lesión intestinal. Mientras que la mayoría de las pruebas detectaron a todos los pacientes con AVT, sólo el 50% de aquellos con histologíanormal tuvieron resultados positivos. Los pacientes con AVP tuvieron resultados discordantes. Así las pruebas clásicas fueron positivas en sólo algunos pacientescon daño leve, mientras que todos ellos fueron positivos a una prueba para detectar ambos isotipos del a-GDP. Conclusión: la determinación de anticuerpos a-GDP fue la herramienta más confiable con el objeto de identificar serológicamente la sensibilidad al gluten en pacientes con DH que presentan variables grados de daño intestinal. Otros estudios deberían explorar si estos hallazgos podrían ser extrapolados a pacientes conEC con enteropatía de grado leve.

Celiac disease serology in dermatitis herpetiformis: which is the best option for detecting gluten sensitivity?

Background: Dermatitis herpetiformis (DH), a wellestablished gluten-sensitive skin disorder presenting variable degrees of enteropathy, constitutes a very useful model in order to assess the utility of the celiac disease (CD)-related serology in patients with mild intestinal damage. Objective: Our aim was to explore comparatively the performance of a panel of CD-related serologic tests in patients with DH. Methods: We assessed a series of 18 consecutive patients with skin biopsy proven DH presenting the overall spectrum of intestinal damage ranging from normal mucosa (n=6) to total villous atrophy (TVA) (n=6) through partial villous atrophy (PVA) (n=6). Sera were obtained from all patients while consuming a gluten containing diet. Serologic tests were antiendomysial, anti-tissue transglutaminase and antigliadin antibodies, and newly developed tests detecting both antibody isotypes (IgA and IgG) against deamidated synthetic gliadin-derivedpeptides (a-GDP). Results: Serologic tests had a variable behaviour depending on the degree of enteropathy. While the majority of tests detected patients with TVA, only 50% of those with normal histology had positive assays. Patients with PVA had discordant results. Classical CD-specific tests were positive in only some patients with mild damage while all of them were identified by a single assay detecting both isotypes of a-GDP. Conclusion: The detection of a-GDP antibodies was the most reliable tool in order to identify gluten sensitivity in DH patients presenting a wide range of intestinal damage. Further studies should explore if these findings can be extrapolated to patients with CDhaving mild enteropathy.(AU)

Introducción: la dermatitis herpetiformis (DH), una lesión dermatológica consecuencia de sensibilidad al gluten y asociada a grados variables de enteropatía, constituye un modelo muy útil con el objeto de evaluar la eficacia de la serología de la enfermedad celíaca(EC) en pacientes con daño intestinal leve. Objetivo: explorar comparativamente la utilidad de una serie de anticuerpos empleados en EC en pacientes con DH. Métodos: analizamos una serie de 18 pacientes consecutivos con diagnóstico de DH por biopsia de piel que presentaban el más amplio espectro de daño intestinal variando desde una mucosa normal (n=6) a la atrofia vellosa total (AVT) (n=6) y pasando por atrofia vellosaparcial (AVP) (n=6). Se obtuvo plasma de todos los pacientes mientras consumían gluten. Las pruebas serológicas empleadas fueron anticuerpos antiendomisio, anti-transglutaminasa y atigliadina, y unas pruebas recientemente desarrolladas que detectan anticuerpos IgA e IgG dirigidos contra péptidos sintéticos deamidados derivados de la gliadina (a-GDP). Resultados: las diferentes pruebas tuvieron un comportamiento variable dependiendo del grado de lesión intestinal. Mientras que la mayoría de las pruebas detectaron a todos los pacientes con AVT, sólo el 50% de aquellos con histologíanormal tuvieron resultados positivos. Los pacientes con AVP tuvieron resultados discordantes. Así las pruebas clásicas fueron positivas en sólo algunos pacientescon daño leve, mientras que todos ellos fueron positivos a una prueba para detectar ambos isotipos del a-GDP. Conclusión: la determinación de anticuerpos a-GDP fue la herramienta más confiable con el objeto de identificar serológicamente la sensibilidad al gluten en pacientes con DH que presentan variables grados de daño intestinal. Otros estudios deberían explorar si estos hallazgos podrían ser extrapolados a pacientes conEC con enteropatía de grado leve.(AU)

Accuracy of testing for antibodies to synthetic gliadin-related peptides in celiac disease.

BACKGROUND & AIMS: Our aim was to explore the diagnostic value of a newly developed synthetic peptide antibody assay addressing specific synthetic gliadin-derived deamidated peptides (AGA II) for the diagnosis of celiac disease (CD). METHODS: We assayed serum samples obtained prospectively at diagnosis from a population of 92 consecutive adult patients with CD and 113 non-CD controls. Patients were reevaluated after 6 months (n = 56) and 1 year (n = 20) of treatment. All patients and controls underwent intestinal biopsy and a set of CD-related serology tests. A newly developed enzyme-linked immunosorbent assay (ELISA) for detecting IgA and IgG antibodies against synthetic deamidated gliadin epitopes was used. RESULTS: At diagnosis, sensitivity and specificity were 94.6% and 99.1% for AGA II IgA and 92.4% and 100% for AGA II IgG. Absolute values and the proportion of positive samples for both antibodies were significantly reduced at 6 months (P < .0000) and 1 year (P < .001) after initiation of a gluten-free diet. Compared with conventional AGA, the peptide antibodies had greater sensitivity, specificity, positive and negative predictive values, accuracy, and likelihood ratios. Compared with antitissue transglutaminase antibodies, AGA II had similar sensitivity but greater specificity and predictive values, better likelihood ratios, and an excellent agreement (kappa statistic = .92). CONCLUSIONS: This study assessed the value of an ELISA assay in detecting antibodies to gliadin-related peptides. This assay appears to be a reliable tool for diagnosing CD and suggests promising accuracy that may be very useful in clinical practice.