Symptoms and signs in individuals with serology positive for celiac disease but normal mucosa

<p>Abstract</p> <p>Background</p> <p>Antibody serology is an important tool in the investigation of celiac disease (CD), but does not always correlate with mucosal appearance in the small intestine. Patients with positive CD serology but normal mucosa (Marsh 0) are at increased risk of future CD. In this study we describe a model for identifying and characterizing individuals with normal mucosa but positive CD serology. Such individuals are sometimes referred to as having latent CD.</p> <p>Methods</p> <p>The records of ten Swedish pathology departments were used to identify individuals with biopsies indicating normal duodenal/jejunal mucosa. Using the national personal identification number, these data were linked with CD serology data (antigliadin, antiendomysial and tissue transglutaminase antibodies); and we thereby identified 3,736 individuals with normal mucosa but positive CD serology. Two independent reviewers then manually reviewed their biopsy reports to estimate comorbidity. We also randomly selected 112 individuals for validation through patient chart review.</p> <p>Results</p> <p>The majority of the 3,736 individuals were females (62%). Children (0–15 years) made up 21.4%. The median number of biopsy specimen was 3. Our review of biopsy reports found that other gastrointestinal comorbidity was rare (inflammatory bowel disease: 0.4%; helicobacter pylori infection: 0.2%). Some 22% individuals selected for patient chart review had a relative with CD. The most common symptoms among these individuals were diarrhea (46%) and abdominal pain (45%), while 26% had anemia. Although 27% of the individuals selected for validation had been informed about gluten-free diet, only 13% were adhering to a gluten-free diet at the end of follow-up.</p> <p>Conclusion</p> <p>Individuals with positive CD serology but normal mucosa often have CD-like symptoms and a family history of CD.</p

Development of an immunocapture method for measuring IgA antibodies to tissue transglutaminase in the sera of patients with coeliac disease

One of the most reliable sero-diagnostic tests for coeliac disease (CD) is the measurement, by ELISA, of serum IgA antibodies to tissue transglutaminase (tTG) adsorbed to the wells of microtitre plates. In spite of its reliability, however, some discrepancies exist with the results obtained by the antiendomysium histological assay (EMA) and by biopsy the accepted gold standard. Among the reasons for these differences in titres between the ELISA and the last 2 mentioned assays are the conformational changes that proteins undergo on adsorption and the importance of conformational epitopes on tTG for diagnosing CD. To address this problem, a novel procedure was developed using guinea-pig tTG (gptTG) free in solution to interact with IgA antibodies in the sera of CD patients. Any immune complexes so formed are then captured by anti-tTG antibodies preadsorbed to the wells of microtitre plates. This immunocapture method was optimized for the amount of soluble gptTG needed to interact with all the IgA's anti-tTG present in fixed dilutions of serum samples, the amount of rabbit IgG anti-gptTG used to coat the wells of microtitre plates and the order of addition of the reaction components. Comparison of the IgA titres obtained by immunocapture with those by EMA and ELISA (adsorbed tTG) on 9 highly positive and 6 weakly positive sera from clinically characterized CD patients and 5 negative sera from non-CD control subjects revealed that the IgA titres by the immunocapture procedure were well correlated with those obtained by EMA, whereas the titres on ELISA showed discrepancies with both immunocapture and EMA