Positive serum antigliadin antibodies without celiac disease in the elderly population: does it matter?

Celiac Disease-Even a Neurological Disorder

Patients with autoimmune rheumatologic conditions and celiac disease tend to have a variety of autoantibodies, many of which have no clear pathogenic role. The literature contains frequent reports of celiac disease being more prevalent in patients with rheumatologic diseases, although this remains controversial. To investigate the prevalence of positive serum tests for celiac disease, particularly IgA and IgG antigliadin (AGA) antibodies and IgA antiendomysium antibodies (EmA) in patients with autoimmune rheumatologic diseases. A second aim was to correlate positive serum tests with prednisone and immunosuppressant medication. A total of 190 adults and pediatric patients with a variety of autoimmune rheumatologic diseases (systemic lupus erythematosus, rheumatoid arthritis, juvenile rheumatoid arthritis and spondyloarthrophathies) were evaluated and tested for IgA and IgG antigliadin-antibodies and IgA antiendomysium antibodies. Patients with positive serum tests underwent endoscopic duodenal biopsies for pathology studies. There were four positive sera (2.1%) for AGA IgA, all of which tested negative for AGA IgG and EmA. Three sera (1.6%) tested positive for AGA IgG; all were negative for AGA IgA and EmA. The EmA test at a 1:2.5 serum dilution tested positive in 94 patients (49.5%); at a 1:5 serum dilution it was positive in 41 patients (21.6%). Eleven subjects tested positive for EmA at 1:40 dilution; and all of these tested negative for IgA tissue antitransglutaminase (tTG) antibodies. Nine of the 11 EmA-positive patients and all 7 patients with positive antigliadin antibodies tests underwent duodenal endoscopic biopsies, and no significant changes were demonstrated in their duodenal mucosa. A positive EmA was associated with elevated optical density AGA IgA readings; however, there was no relationship between positive EmA and AGA IgG optical density readings. Prednisone and immunosuppressant use were unrelated to AGA IgA optical density readings or AGA IgG readings. These drugs were associated with fewer positive EmA tests. Positive AGAA, AGAG or EmA results are probably nonspecific for the presence of celiac disease among autoimmune rheumatologic disease patients. The intake of prednisone and immunosuprressant drugs seems to reduce the prevalence of IgA EmA, but it does not interfere with antigliadin antibodies tests.Further studies are required to estimate more accurately the prevalence of this disease in rheumatologic patients.

The diagnostic accuracy of serologic tests for celiac disease: A systematic review

<h3>Introduction</h3> The use of anti-gliadin antibodies (AGA) and anti-endomysial antibodies (EMA) is well established as a means of screening for coeliac disease (CD). Since the presence of EMA is highly specific for CD, a negative EMA result may deter some doctors from referring patients with positive AGA for duodenal (D2) biopsy or gastroenterological assessment. In CD there is a prevalence of IgA deficiency of around 3%, with corresponding negative EMA. In addition, isolated positive AGA are found in other gastrointestinal (GI) conditions, such as Crohn9s disease and chronic liver disease. <h3>Methods</h3> Aims: (1) To determine the proportion of patients with positive IgG AGA and/or IgA AGA but negative EMA who had undergone endoscopy and D2 biopsy. (2) To invite those who had not been investigated to attend either the gastroenterology clinic or for direct endoscopy and duodenal biopsy. (3) To determine the prevalence of CD and other gastrointestinal pathology. We identified patients with positive IgG and/or IgA AGA but negative EMA from the pathology database from February 2007 to August 2008. The medical records were reviewed to determine if there were features of CD on duodenal biopsy if performed, or alternative GI diagnoses. We wrote to the referring doctor and the general practitioner, requesting referral to gastroenterology if D2 biopsy had not been undertaken. If no reply, we contacted the patient directly. <h3>Results</h3> 1597 requests for coeliac serology were made during the 18 months: 186 were both AGA and EMA positive. Forty-six patients were AGA positive with negative EMA: 24 had undergone D2 biopsy; 2 had died prior to further investigation (86 and 89 years old); 1 was ineligible for NHS care; 1 patient had no contact details; and 1 patient had repeat EMA and AGA, which were negative. Of the remaining 17 patients, 8 agreed to undergo OGD and D2 biopsy. <h3>Conclusion</h3> CD is not uncommonly present in patients with isolated positive AGA and all such patients should be referred for OGD and D2 biopsy. Further investigation should also be considered as other gastrointestinal disorders are prevalent in these patients, probably in part reflecting the presence of symptoms or abnormal blood tests that prompted the request for AGA. The majority of requests for coeliac serology originate from primary care or non-GI physicians, many of whom fail to appropriately follow-up positive AGA. Laboratories should consider providing advice on AGA interpretation with test results.

Follow-up of patients with celiac disease: Achieving compliance with treatment

Screening test for coeliac disease

Celiac disease: an emerging global problem.

The use of immunoglobulin G and A anti-gliadin antibodies for celiac disease screening has decreased due to higher specificity and sensitivity of tissue transglutaminase and endomysial antibodies. Greater values of immunoglobulin-A anti-gliadin antibody have been associated with more severe mucosal damage in proven and probable celiac disease patients. The aim of this study was to determine whether anti-gliadin antibody immunoglobulin A has any clinical importance in diagnosing celiac disease in children. Children with a chronic history of vomiting, abdominal pain, diarrhea, or constipation in the outpatient clinic were evaluated for celiac disease. Tissue transglutaminase and anti-gliadin antibody immunoglobulin A in serum were determined by ELISA test and endomysial antibodies immunoglobulin A by indirect immunofluorescence. Most of these children with isolated positive anti-gliadin antibody immunoglobulin A were further evaluated by performing proximal gastrointestinal biopsies. Sixteen children had isolated positive anti-gliadin antibody immunoglobulin A (negative tissue transglutaminase and endomysial antibodies immunoglobulin A). Eight were male (mean age: 9.7 years). None had immunoglobulin A deficiency. Thirteen underwent an upper endoscopy with multiple small bowel biopsies. Two patients had villous atrophy and slightly increased intraepithelial lymphocytes (Marsh 3a), which could make the diagnosis of celiac disease likely. These two patients had high titers of anti-gliadin antibody immunoglobulin A above 70 Units. An isolated positive antigliadin antibody immunoglobulin A result in the absence of positive tissue transglutaminase and endomysial antibodies immunoglobulin A should raise the suspicion of the diagnosis of celiac disease. This could be a non-specific phenomenon that could be found in other gastrointestinal conditions, latent celiac disease, or gluten hypersensitivity. A longitudinal clinical follow-up is recommended in these children to confirm the diagnosis.

<h3>Introduction</h3> Coeliac disease (CD) and irritable bowel syndrome (IBS) may share similar symptoms, including bloating, abdominal pain, and diarrhoea. A previous meta-analysis demonstrated the prevalence of CD was higher in patients with IBS than controls without IBS, but recent studies have cast doubt on this. We therefore updated our previous meta-analysis. <h3>Methods</h3> MEDLINE and EMBASE were searched from 2008 (the date of a previous meta-analysis) up to February 2016. Relevant case series and case-control studies with unselected adults with IBS (+/- controls) were reviewed. IBS diagnosis was based on specific symptom-based criteria, physician’s opinion, or questionnaire data. Tests for CD included IgA antigliadin antibodies (AGA), tissue transglutaminase antibodies (tTG), endomysial antibodies (EMA), or dudoenal (D2) biopsies after positive IgA AGA, tTG, or EMA. The proportion of individuals meeting criteria for IBS testing positive for CD was combined, to give a pooled prevalence in all studies. For case-control studies the prevalence of a positive test for CD in both cases with IBS and controls without IBS were compared using odds ratios (OR) with a 95% confidence interval (CI). <h3>Results</h3> 10 studies used IgA AGAs to screen for CD in 4525 subjects, 2094 of whom had IBS. Pooled prevalence of positive IgA AGAs in IBS subjects was 5.7% (95% CI 1.7% to 11.8%). 7 of these were case-control studies and the odds ratio for a positive IgA AGA in 1530 IBS cases, compared with 2430 controls, was 2.97 (95% CI 1.42 to 6.18). 32 studies used EMA or tTG in 14150 subjects, 8219 of whom had IBS. Pooled prevalence of positive EMA or tTG was 2.6% (95% CI 1.6% to 3.8%). 12 of these were case-control studies and the odds ratio for a positive EMA or tTG in the 2677 IBS cases compared with 5931 controls was 2.60 (95% CI 1.41 to 4.79). 23 studies followed positive coeliac serology of any type with the offer of duodenal biopsy in 9784 individuals, 6991 of whom met criteria for IBS. Pooled prevalence of biopsy-proven CD in these studies was 3.3% (95% CI 2.3% to 4.5%). 8 of these were case-control studies and the odds ratio for biopsy-proven CD in 2025 IBS subjects compared with 2793 controls was 3.96 (95% CI 2.06 to 7.59). <h3>Conclusion</h3> Screening for CD in people with symptoms compatible with IBS is still worthwhile. Between 2.6% and 5.7% will have a positive serological test for CD, and 3.3% will have biopsy-proven CD. In all instances, the prevalence was significantly higher than in controls without IBS-type symptoms. <h3>Disclosure of Interest</h3> None Declared

What Is the Role of Serologic Testing in Celiac Disease? A Prospective, Biopsy-Confirmed Study With Economic Analysis

Tu1432 A Longitudinal Study of Clinical Parameters and Cytokine Profiles in IBS

Celiac disease screening: exploring the iceberg with salivary antigliadin antibodies.

To establish the prevalence of coeliac disease in the general population and in specific conditions, such as irritable bowel syndrome, iron deficiency anaemia, fatigue and other coeliac-related conditions. Primary-care-based cross-sectional study using immunoglobulins, IgA/IgG antigliadin antibodies and endomysial antibodies to initially recognize coeliac disease. A total of 1200 volunteers were recruited from January 1999 to June 2001 from five general practices in South Yorkshire, UK. Any participant with a positive IgA antigliadin antibody, positive endomysial antibody, or only IgG antigliadin antibody in the presence of IgA deficiency was offered a small-bowel biopsy to confirm the diagnosis of coeliac disease. Twelve new cases of coeliac disease were diagnosed from 1200 samples. The prevalence of coeliac disease in this primary care population sample is 1% (95% CI 0.4-1.3%). The prevalence of coeliac disease was 3.3% (4/123) in participants with irritable bowel syndrome, 4.7% (3/64) in participants with iron deficiency anaemia, and 3.3% (3/92) in participants with fatigue. This study describes the prevalence of undiagnosed adult coeliac disease in primary care patients with irritable bowel syndrome, iron deficiency anaemia and fatigue. Underdiagnosis of coeliac disease is common in primary care. A case-finding approach would avoid delays in diagnosis and the associated morbidity or potential complications of coeliac disease. A low threshold for serological screening of patients with coeliac-associated symptoms or conditions would be an optimal strategy.

To evaluate the effect of gluten free diet (GFD) on magnetic resonance spectroscopy (MRS) of the cerebellum in patients with gluten ataxia (GA). Patients with GA, defined as sporadic ataxia with positive antigliadin antibodies in the absence of an alternative cause, routinely undergo MRS at baseline and after the introduction of GFD as part of their clinical care. We present our experience of the effect of GFD on MRS of the cerebellum. A total of 117 consecutive patients with GA were included in this report. Sixty-three were on strict GFD with elimination of antigliadin antibodies, 35 were on GFD but were still positive for antigliadin antibodies, and 19 patients opted not to go on GFD. The N-acetylaspartate (NAA)/creatine (Cr) area ratio from the cerebellar vermis increased in 62 out of 63 (98%) patients on strict GFD, in 9 of 35 (26%) patients on GFD but positive antibodies, and in only 1 of 19 (5%) patients not on GFD. The NAA/Cr ratio decreased in all 14 ataxia control patients (cerebellar variant of multisystem atrophy). There were no differences in the MRS results between those patients who had and those who did not have enteropathy (celiac disease) within each group. The demonstration of increased NAA/Cr ratio on repeat scanning following strict GFD strengthens previous findings of clinical improvement of the ataxia in patients with GA. The presence of enteropathy is not a prerequisite for such improvement; therefore patients with positive serology and negative duodenal biopsy should still be treated with strict GFD.

We analyze the diagnostic efficacy of two celiac disease serological markers: anti-gliadin (IgA and IgG class) and anti-endomysium IgA-class (EmA-IgA) antibodies applied to 336 serum samples from celiac patients on both gluten-challenge and gluten-free diets, and a control group. The anti-gliadin and anti-endomysium antibodies levels were significantly higher among the gluten-consuming celiac patients than in the other groups. The greatest efficacy in diagnosing celiac disease was achieved in the Ema-IgA class test. The IgA-class anti-gliadin antibodies proved to be more specific, with a higher positive test predictive value than the IgG-class anti-gliadin antibodies, whereas the latter proved to be more sensitive, with a higher negative test predictive value than those of the IgA-class anti-gliadin antibodies. Our results also demonstrate that the simultaneous assessment of anti-gliadin IgA- and IgG-class antibodies constitutes a valid test in selecting patients suspected of having celiac disease. In turn the EmA-IgA antibodies constitute a confirmative test for indication of an intestinal biopsy.