Gluten-Free Diet Reduces Symptoms, Particularly Diarrhea, in Patients With Irritable Bowel Syndrome and Antigliadin IgG.

BACKGROUND & AIMS: Many patients with irritable bowel syndrome (IBS) perceive that their symptoms are triggered by wheat-containing foods. We assessed symptoms and gastrointestinal transit before and after a gluten-free diet (GFD) in unselected patients with IBS and investigated biomarkers associated with symptoms. METHODS: We performed a prospective study of 50 patients with IBS (ROME III, all subtypes), with and without serologic reactivity to gluten (antigliadin IgG and IgA), and 25 healthy subjects (controls) at a university hospital in Hamilton, Ontario, Canada, between 2012 and 2016. Gastrointestinal transit, gut symptoms, anxiety, depression, somatization, dietary habits, and microbiota composition were studied before and after 4 weeks of a GFD. HLA-DQ2/DQ8 status was determined. GFD compliance was assessed by a dietitian and by measuring gluten peptides in stool. RESULTS: There was no difference in symptoms among patients at baseline, but after the GFD, patients with antigliadin IgG and IgA reported less diarrhea than patients without these antibodies (P = .03). Compared with baseline, IBS symptoms improved in 18 of 24 patients (75%) with antigliadin IgG and IgA and in 8 of 21 patients (38%) without the antibodies. Although constipation, diarrhea, and abdominal pain were reduced in patients with antigliadin IgG and IgA, only pain decreased in patients without these antibodies. Gastrointestinal transit normalized in a higher proportion of patients with antigliadin IgG and IgA. Anxiety, depression, somatization, and well-being increased in both groups. The presence of antigliadin IgG was associated with overall reductions in symptoms (adjusted odds ratio compared with patients without this antibody, 128.9; 95% CI, 1.16-1427.8; P = .04). Symptoms were reduced even in patients with antigliadin IgG and IgA who reduced gluten intake but were not strictly compliant with the GFD. In controls, a GFD had no effect on gastrointestinal symptoms or gut function. CONCLUSIONS: Antigliadin IgG can be used as a biomarker to identify patients with IBS who might have reductions in symptoms, particularly diarrhea, on a GFD. Larger studies are needed to validate these findings. ClinicalTrials.gov: NCT03492333.

The Significance of Low Titre Antigliadin Antibodies in the Diagnosis of Gluten Ataxia.

BACKGROUND: Patients with gluten ataxia (GA) without enteropathy have lower levels of antigliadin antibodies (AGA) compared to patients with coeliac disease (CD). Magnetic Resonance Spectroscopy (NAA/Cr area ratio) of the cerebellum improves in patients with GA following a strict gluten-free diet (GFD). This is associated with clinical improvement. We present our experience of the effect of a GFD in patients with ataxia and low levels of AGA antibodies measured by a commercial assay. METHODS: Consecutive patients with ataxia and serum AGA levels below the positive cut-off for CD but above a re-defined cut-off in the context of GA underwent MR spectroscopy at baseline and after a GFD. RESULTS: Twenty-one consecutive patients with GA were included. Ten were on a strict GFD with elimination of AGA, 5 were on a GFD but continued to have AGA, and 6 patients did not go on a GFD. The NAA/Cr area ratio from the cerebellar vermis increased in all patients on a strict GFD, increased in only 1 out of 5 (20%) patients on a GFD with persisting circulating AGA, and decreased in all patients not on a GFD. CONCLUSION: Patients with ataxia and low titres of AGA benefit from a strict GFD. The results suggest an urgent need to redefine the serological cut-off for circulating AGA in diagnosing GA.

Pentraxin 3 and biopsy status in celiac patients.

AIM: In our study we explored a possible relationship between PTX3 and CD. BACKGROUND: Gluten sensitivity is known as a hallmark of celiac disease (CD). The diagnosis of CD requires demonstration of a typical enteropathy, and positive serology supports the diagnosis. The CD immune response involves the adaptive, as well as the innate immunity and is characterized by the presence of anti-gliadin (AGA) and anti-transglutaminase 2 antibodies (tTGA), lymphocytic infiltration in the intestinal epithelial membrane and expression of multiple cytokines. The long pentraxin 3 (PTX3), an acute-phase inflammatory molecule, plays an important role in innate immunity. METHODS: 108 CD patients were divided according to Marsh Histological grade following Marsh criteria classification in three groups: Group 1: Marsh 0, patients with a known history of CD under gluten free diet, complete remission; Group 2: Marsh1 and Marsh 2; Group 3: Marsh 3. Healthy age-matched controls without a known history of CD or gastrointestinal symptoms (n=30) served as controls. PTX3 serum levels were measured by sandwich ELISA on an automated platform. RESULTS: PTX3 serum levels were significantly elevated in group 3 and group 2 compared with HC (mean 3.31± 1.27 ng/mL and 3.97 ± 0.54 ng/mL versus 1.06 ± 0.59 ng/mL; P < 0.005), with group 1 (0.76±0.31 ng/mL). No statistically significant differences were found between group 1 and HC group. We found a strong linear correlation between PTX3 serum levels and AGA levels in group 2 (r=0.78, P <0.0001), and group 3 (r =0.63, P < 0.005) but no correlations were detected between PTX3 serum levels and tTGA levels (group 2, r= 0.04; group 3, r=0.24). Serological data revealed that PTX3 correlated with major gastrointestinal damage patients. CONCLUSION: PTX3 is a component of the humoral arm of the innate immune system. Our data showed that PTX3 serum levels were high in active disease patients with pathological levels of AGA. We also demonstrated that patients with normal AGA IgA levels had PTX3 serum levels compared to healthy control. We hypothesized that PTX3 is able to modulate the innate response to gliadin in CD and it could regulate the adaptive immune response.

Prevalence of antigliadin IgA antibodies in psoriasis vulgaris and response of seropositive patients to a gluten-free diet.

INTRODUCTION: The course of psoriasis relies on a variety of metabolic and immunological parameters. Identification of underlying pro-inflammatory conditions and their control is desired for optimal management. BACKGROUND: Increased prevalence of serum markers for celiac disease has been reported among patients with psoriasis. The likelihood of occult celiac disease in a subpopulation of patients has been postulated and gluten-free diets have been reported to be effective. PATIENTS AND METHODS: The prevalence of gliadin IgA antibodies was assessed among patients with psoriasis in an urban population. The clinical effects of a strict gluten-free diet were followed. RESULTS: Over a 2-year period, 97 patients with Psoriasis Area and Severity Index greater than 2.4 were recruited from a population followed in a dermatology clinic. Gliadin IgA antibodies were assessed in all participants and in 91 controls. Elevated gliadin IgA antibodies were found in 13 patients (14%) and two controls (2%). Values in five patients were assessed as greater than 30.0 U/mL or "strong positive" according to the manufacturer of the assay. All 13 patients were placed on a strict gluten-free diet without any other modifications in their ongoing treatment of psoriasis. Improvement of psoriatic lesions was observed in all patients with positive gliadin IgA antibodies but the decline in the Psoriasis Area and Severity Index score and the scaling down of pharmaceutical treatment was more pronounced in the five patients with strong positive gliadin IgA indicating an immune aberration amenable to diet changes. CONCLUSION: Prevalence of antigliadin IgA antibody is significant among patients with psoriasis not diagnosed with celiac disease or non-celiac gluten sensitivity. For all its limitations, antigliadin IgA testing can identify patients likely to benefit from gluten-free diets.

Diagnostic accuracy of anti-gliadin antibodies in Non Celiac Gluten Sensitivity (NCGS) patients: A dual statistical approach.

BACKGROUND: Gluten is the target of several diseases such as wheat allergy (WA), celiac disease (CD) and non-celiac gluten sensitivity (NCGS). NCGS is a new clinical entity characterized by gastrointestinal and extraintestinal symptoms comparable to those of CD patients but to date still lacking of specific biomarkers so that NCGS diagnosis can be reached only by excluding CD and WA, and based on the direct association between gluten ingestion and symptoms onset. Previous studies showed that antigliadin antibodies (AGA) IgG are the most prevalent positive antibodies in NCGS population. AIM: The first aim of the study was to estimate AGA distribution and prevalence in a NCGS population. The second aim was to identify a serological pattern to help the diagnosis and/or to mark the NCGS disease. METHODS: Sera from 59 patients with suspected NCGS, 90 CD patients and 70 healthy individuals were assessed for AGA IgG/IgA, IgG/IgA deamidated gliadin peptide antibodies (DGP-AGA), tissue transglutaminase antibodies IgA (tTGA), endomysial antibodies IgA (EmA) and HLA typing (Eurospital, Trieste, Italy). RESULTS: We evaluated data by a dual statistical approach: logistic regression and receiver operating characteristic (ROC) analysis; therefore, we showed a poor diagnostic accuracy of AGA IgG in NCGS condition. CONCLUSION: Our preliminary data showed that AGA IgG didn't seem to be a strongly sensitive marker, even if it has been recently proposed as promising marker for NCGS condition, together with negativity for other celiac disease related antibodies. It can partially help the NCGS diagnosis, if it is integrated in the overall management of the patient. More in-depth clinical and laboratory researches are mandatory.

Sensibilidad y especificidad de los marcadores serológicos para diagnóstico y seguimiento de la condición celíaca / Sensitivity and specificity of serological markers for diagnosis and monitoring of celiac condition

Introducción: El diagnóstico precoz y seguimiento de la condición celíaca ha sido objeto de importantes cambios, y según la guía ESPGHAN (2012) la serología es ahora una herramienta fundamental. Los principales son los anticuerpos anti-gliadina IgG/IgA, anti-transglutaminasa IgG/IgA, anti-endomisiales (EMA), y los recientemente descritos anti-péptidos deaminados de gliadina (anti-DGPs). El propósito del estudio fue determinar la sensibilidad y especificidad de estos marcadores en 308 individuos con y sin patología. Materiales y métodos: A cada individuo se le realizaron determinaciones de: TTGG y TTGA Qual (AESKU Diagnostics ®, Germany), TgTG, TgTA, AAGG y AAGA por ENEASYSTEM III® (Byogenetix, Italia), Neoep. IgG/A (AESKU Diagnostics®, Germany), EMA IgG e IGA y GAF3X IgG e IgA (Euroimmun, Germany ®). Resultados: Los valores de sensibilidad (S) y especificidad (E) fueron: Para anti-IgA Celicheck: S: 44.44%, E: 97.59%; anti-TTG Qual: S: 14.28%, E: 97.61%; anti-neoepítopes IgG/IgA: S: 54.44%, E: 91.59%; AAG IgG: S: 89.11%, E: 63.19%; AAG IgA: S: 79.11%, E: 68.16%; anti-DGPs IgA: S: 86.67%, E: 96.21% (p<0,05). Conclusiones: Los ATgT IgG e IgA solo son superados por los anti-DGPs. Se debe ampliar las investigaciones para estandarizar este nuevo método de valoración.

Introduction: The diagnosis and management of celiac disease has undergone significant changes, according to the ESPGHAN guide (2012) serology is now an essential tool. The main ones are the anti-gliadin IgG/IgA anti-transglutaminase IgG/IgA, anti-endomysial and the recently described anti-deaminated gliadin peptides (anti-DGPs). The purpose of the study was to determine the sensitivity and specificity of these markers in 308 individuals with and without pathology. Materials and Methods: Each individual is simultaneously made the following determinations: TTGG and TTGA Qual (AESKU Diagnostics®, Germany), TgTG, TgTA, AAGG and AAGA ENEASYSTEM III® (Byogenetix, Italia), Neoep. IgG/A (AESKU Diagnostics®, Germany), EMA IgG, IGA and GAF3X IgG-IgA (Euroimmun, Germany®). Results: The sensitivity (S) and specificity (Sp) were: anti-IgA To Celicheck: S: 44.44%, E: 97.59% anti-TTG Qual: S: 14.28%, E: 97.61% anti-neoepitopes IgG/IgA: S: 54.44%, E: 91.59%; AAG IgG: S: 89.11%, E: 63.19%; AAG IgA: S: 79.11%, E: 68.16% IgA anti-DGPs: S: 86.67% E: 96.21% (p<0.05). Conclusions: IgG and IgA ATGT are surpassed only by anti-DGPs However, it is important to extend the research to standardize this new method of assessment.

Gluten-related neurologic dysfunction.

The term gluten-related disorders (GRD) encompasses a spectrum of systemic autoimmune diseases with diverse manifestations. GRD are characterized by abnormal immunological responsiveness to ingested gluten in genetically susceptible individuals. Celiac disease (CD) or gluten-sensitive enteropathy is only one of a number of GRD. Extraintestinal manifestations include dermatitis herpetiformis (DH) and neurologic dysfunction. Furthermore it is only recently that the concept of extraintestinal manifestations without enteropathy has become accepted. In this chapter we review the spectrum of neurologic manifestations in GRD, discuss recent advances in their diagnosis, and look at their possible pathophysiologic mechanisms.

Gliadin does not induce mucosal inflammation or basophil activation in patients with nonceliac gluten sensitivity.

BACKGROUND & AIMS: Nonceliac gluten-sensitive (NCGS) patients report intestinal and extra-intestinal symptoms shortly after ingesting gluten; these symptoms disappear on gluten-free diets, although these patients have no serologic markers of celiac disease or intestinal damage. In fact, there is no evidence for mucosal or serologic modifications in those individuals. We investigated immunologic responses of duodenal mucosa samples and peripheral blood basophils, isolated from NCGS patients, after exposure to gliadin. METHODS: Participants underwent a complete clinical evaluation to exclude celiac disease while on a gluten-containing diet, a skin prick test to exclude wheat allergy, and upper endoscopy (n = 119) at 2 tertiary medical centers in Italy. Patients were considered to have NCGS based on their symptoms and the current definition of the disorder. Subjects were assigned to the following groups: patients with celiac disease on gluten-free diets (n = 34), untreated patients with celiac disease (n = 35), patients with NCGS (n = 16), or controls (n = 34). Duodenal biopsy samples collected during endoscopy were incubated with gliadin peptides, and levels of inflammatory markers were assessed. Peripheral blood basophils were extracted and incubated with gliadin peptides or a mix of wheat proteins; activation was assessed based on levels of CD203c, CD63, and CD45. RESULTS: Duodenal mucosa samples collected from 69 patients with celiac disease showed markers of inflammation after incubation with gliadin. Some, but not all, markers of inflammation were detected weakly in biopsy samples from 3 controls and 3 NCGS patients (P = .00 for all markers). There were no significant increases in the levels of CD63 and CD203c in NCGS patients. CONCLUSIONS: Unlike the duodenal mucosa from patients with celiac disease, upon incubation with gliadin, mucosa from patients with NCGS does not express markers of inflammation, and their basophils are not activated by gliadin. The in vitro gliadin challenge therefore should not be used to diagnose NCGS.

Association between Celiac Disease and Chronic Hepatitis C Virus Infection.

Celiac disease affects the proximal small intestine and is caused by a local immune response to dietary gluten. Celiac disease usually presents with chronic diarrhea; however, presentations with elevated hepatic transaminase levels in blood or with iron-deficiency anemia have been described. Celiac disease has been reported to be associated with autoimmune liver diseases. Hepatitis C virus (HCV) can also initiate autoimmune disease process. Therefore, HCV infection and celiac disease may occur together. Here, we describe 4 cases of celiac disease associated with chronic hepatitis C. This small case series indicates that chronic HCV infection and celiac disease are not causally associated.

Antigliadin antibodies in Spinocerebellar AtaxiaType 2 Cuban patients

The relevance of gluten sensitivity in hereditary ataxia pathogenesis is unclear. To evaluate the significance of antigliadin antibodies levels forspinocerebellar ataxia type 2. We determined antigliadin antibodies in 64 spinocerebellar ataxia type 2 patients and in 65 healthy matched controls. The clinical assessment was carried out using the International Cooperative Ataxia Rating Scale and CAG repeat number was assessed by PCR. Results: Antibodies were positive in 23,4 percent of the ataxia patients and 9,09 percent of the controls. Statistical comparison using (chi)2 test with Yatess correction reveal significant differences between these two groups ( 2 3,94; p 0,047). The same was obtained for strongly positive antigliadin antibodies ( 2 4,62; p 0,032). There were not significant differences between AGA positive and AGA negative patients in age at onset, disease duration, ataxia score, or CAG repeat number;neither in the prevalence of gastrointestinal symptoms, prevalence of wheat intolerance,or body weight. These results demonstrates an association between antigliadin antibodies serum levels and SCA2. However, more work has to be done to clarify the clinical consequences of such an association...(AU)

Celiac disease associated antibodies in persons with latent autoimmune diabetes of adult and type 2 diabetes

Background: Celiac Disease (CD) is present in 1–16.4 percent of patients with type 1 diabetes mellitus. The most important serological markers of CD are anti-endomysial (EMA), anti-tissue transglutaminase (tTGA) and antigliadin antibodies (AGA). Aim/hypothesis: The objective of this work is to determine the frequency of tTGA and/or AGA in latent autoimmune diabetes of adult (LADA) and subjects with type 2 diabetes (T2DM), as well as to evaluate their relation with several clinical and biochemical characteristics. Subjects and Methods: Forty three subjects with LADA and 99 with T2DM were studied. The presence of AGA, tTGA was determined in the sera of these patients. The variables: sex, age, duration of diabetes, treatment, body mass index (BMI) and fasting blood glucose concentration were also recorded. Results: No differences were found in the frequency of celiac disease associated antibodies between LADA and T2DM subjects. The presence of celiac disease related antibodies was more frequent in patients with a normal or low BMI. Conclusions: Celiac disease does not seem to be related with pancreatic autoimmunity in type 2 diabetes. Celiac disease causes a decrease of body mass index in type 2 diabetes while pancreatic islet autoimmunity in this entity masks this eft(AU)