A Prospective Study on Cognitive Impairment in Middle-aged Adults With Newly Diagnosed Celiac Disease.

AIMS: Our objectives were to: (1) determine whether celiac disease (CD) patients have cognitive impairment at diagnosis; and (2) compare their cognitive performance with nonceliac subjects who have similar chronic symptoms and healthy controls. MATERIALS AND METHODS: Fifty adults (age range: 18 to 50 y) with symptoms and signs compatible with CD were enrolled in a prospective cohort irrespective of the final diagnosis. At baseline, all individuals underwent cognitive functional and psychological evaluation. CD patients were compared with subjects in whom CD was ruled out and with healthy controls matched by sex, age, and years of schooling. RESULTS: Thirty-three subjects (66%) were diagnosed with CD. Compared with the healthy controls (n=26), CD cases and disease controls (n=17; mostly irritable bowel syndrome) had impaired cognitive performance (P=0.02 and P=0.04, respectively), functional impairment (P<0.01), and higher depression (P<0.01). CD patients had similar cognitive performance and anxiety, but nonsignificant lower depression scores compared with disease controls. CONCLUSIONS: Abnormal cognitive functions detected in newly diagnosed CD adult patients seem not to be disease specific. Our results suggest that cognitive dysfunction could be related to the presence of prolonged symptoms due to a chronic disease.

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.

Altered Esophageal Mucosal Structure in Patients with Celiac Disease.

Background/Aim. Reflux symptoms (RS) are common in patients with celiac disease (CD), a chronic enteropathy that affects primarily the small intestine. We evaluated mucosal integrity and motility of the lower esophagus as mechanisms contributing to RS generation in patients with CD. Methods. We enrolled newly diagnosed CD patients with and without RS, nonceliac patients with classical reflux disease (GERD), and controls (without RS). Endoscopic biopsies from the distal esophagus were assessed for dilated intercellular space (DIS) by light microscopy and electron microscopy. Tight junction (TJ) mRNA proteins expression for zonula occludens-1 (ZO-1) and claudin-2 and claudin-3 (CLDN-2; CLDN-3) was determined using qRT-PCR. Results. DIS scores were higher in patients with active CD than in controls, but similar to GERD patients. The altered DIS was found even in CD patients without RS and normalized after one year of a gluten-free diet. CD patients with and without RS had lower expression of ZO-1 than controls. The expression of CLDN-2 and CLDN-3 was similar in CD and GERD patients. Conclusions. Our study shows that patients with active CD have altered esophageal mucosal integrity, independently of the presence of RS. The altered expression of ZO-1 may underlie loss of TJ integrity in the esophageal mucosa and may contribute to RS generation.

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.

Significant bone microarchitecture impairment in premenopausal women with active celiac disease.

Patients with active celiac disease (CD) are more likely to have osteoporosis and increased risk of fractures. High-resolution peripheral quantitative computed tomography (HR-pQCT) permits three-dimensional exploration of bone microarchitectural characteristics measuring separately cortical and trabecular compartments, and giving a more profound insight into bone disease pathophysiology and fracture. We aimed to determine the volumetric and microarchitectural characteristics of peripheral bones-distal radius and tibia-in an adult premenopausal cohort with active CD assessed at diagnosis. We prospectively enrolled 31 consecutive premenopausal women with newly diagnosed CD (median age 29 years, range: 18-49) and 22 healthy women of similar age (median age 30 years, range 21-41) and body mass index. Compared with controls, peripheral bones of CD patients were significantly lower in terms of total volumetric density mg/cm(3) (mean ± SD: 274.7 ± 51.7 vs. 324.7 ± 45.8, p 0.0006 at the radius; 264.4 ± 48.7 vs. 307 ± 40.7, p 0.002 at the tibia), trabecular density mg/cm(3) (118.6 ± 31.5 vs. 161.9 ± 33.6, p<0.0001 at the radius; 127.9 ± 28.7 vs. 157.6 ± 15.6, p < 0.0001 at the tibia); bone volume/trabecular volume ratio % (9.9 ± 2.6 vs. 13.5 ± 2.8, p<0.0001 at the radius; 10.6 ± 2.4 vs. 13.1 ± 1.3, p < 0.0001 at the tibia); number of trabeculae 1/mm (1.69 ± 0.27 vs. 1.89 ± 0.26, p 0.009 at the radius; 1.53 ± 0.32 vs. 1.80 ± 0.26, p 0.002 at the tibia); and trabecular thickness mm (0.058 ± 0.010 vs. 0.071 ± 0.008, p < 0.0001 at the radius with no significant difference at the tibia). Cortical density was significantly lower in both regions (D comp mg/cm(3) 860 ± 57.2 vs. 893.9 ± 43, p 0.02; 902.7 ± 48.7 vs. 932.6 ± 32.6, p 0.01 in radius and tibia respectively). Although cortical thickness was lower in CD patients, it failed to show any significant inter-group difference (a-8% decay with p 0.11 in both bones). Patients with symptomatic CD (n = 22) had a greater bone microarchitectural deficit than those with subclinical CD. HR-pQCT was used to successfully identify significant deterioration in the microarchitecture of trabecular and cortical compartments of peripheral bones. Impairment was characterized by lower trabecular number and thickness-which increased trabecular network heterogeneity-and lower cortical density and thickness. In the prospective follow-up of this group of patients we expect to be able to assess whether bone microarchitecture recovers and to what extend after gluten-free diet.

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).

Risk of fracture in celiac disease: gender, dietary compliance, or both?

AIM: To determine the incidence of peripheral fractures in patients with celiac disease (CD) and the effect of treatment on fracture risk. METHODS: We compared the incidence and risk of peripheral fractures before and after diagnosis between a cohort of 265 patients who had been diagnosed with CD at least 5 years before study entry and a cohort of 530 age- and sex-matched controls who had been diagnosed with functional gastrointestinal disorders. Data were collected through in-person interviews with an investigator. The overall assessment window for patients was 9843 patient-years (2815 patient-years after diagnosis). RESULTS: Compared with the control group, the CD cohort showed significantly higher incidence rate and risk of first peripheral fracture before diagnosis [adjusted hazard ratio (HR): 1.78, 95% CI: 1.23-2.56, P < 0.002] and in men (HR: 2.67, 95% CI: 1.37-5.22, P < 0.004). Fracture risk was significantly associated with the classic CD presentation with gastrointestinal symptoms (P < 0.003). In the time period after diagnosis, the risk of fractures was comparable between the CD cohort and controls in both sexes (HR: 1.08, 95% CI: 0.55-2.10 for women; HR: 1.57, 95% CI: 0.57-4.26 for men). CONCLUSION: CD patients have higher prevalence of fractures in the peripheral skeleton before diagnosis. This is associated with male sex and classic clinical presentation. The fracture risk was reduced after the treatment.

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.

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.

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.

Very high rate of misdiagnosis of celiac disease in clinical practice.

OBJECTIVE: We evaluated the accuracy of the diagnosis of celiac disease (CD) performed in the community clinical setting compared with that of an academic experienced center. MATERIALS: Original biopsy slides and reports used for diagnosis in the community setting and the CD serology were revised in 70 consecutive patients attending our institution for a second opinion. An expert team determined the final diagnosis unaware of the original consideration. RESULTS: The poor quality of samples made histology assessment by the expert pathologist uncertain in 8.7% of slides with CD external diagnosis. We detected a divergent diagnosis between the two practice settings in 46.3% of available cases with a significant overdiagnosis of CD in the community (p < 0.0001). Congruent serology results were demonstrated in 72.2% of cases. CONCLUSION: Our study detected a high rate of histopathological and serological misdiagnosis of CD in community practice which may have profound negative impact on patients.

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.

Clinical utility of counting intraepithelial lymphocytes in celiac disease intestinal mucosa.

BACKGROUND/AIMS: Our aims were to establish the clinical utility of assessing the intraepithelial lymphocyte (IEL) density in intestinal biopsies from a large series of individuals and to determine the best threshold discriminating celiac disease (CD) patients and controls in two populations with different pre-test prevalence. METHODS: We prospectively performed intestinal biopsy and CD-related serology in 349 subjects undergoing upper GI endoscopy. While 116 had symptoms suggestive of a small bowel disorder (high prevalence), 233 individuals were randomly selected from patients referred to endoscopy because upper GIsymptoms (low prevalence). Diagnosis of CD was based on the concordance of classical histological features and a positive CD serology. RESULTS: While 58 patients had a newly diagnosed CD (52 in the high and 6 in the low prevalence groups), 291 subjects did not meet diagnostic criteria of the disorder. Patients had a highly significant greater IEL density than controls (p < 0.00001). Based on the ROC curve, a count of 22.8 IEL/100 epithelial cells had the highest performance for diagnosing CD in the overall population and for subjects in the high pre-test probability subgroup and 22.5% was ,he best cut-off for those diagnosed in the low risk population (area under the curves: 0.979, 0.979 and 0.993, respectively). An abnormal CD serology confirmed the diagnosis of CD in all the four patients with counts below 22.8%. CONCLUSIONS: Our study confirms that an IEL density of 22.8% is an adequate threshold to discriminate CD patients and controls in individuals irrespective of the prevalence of the disorder.