Anti‐gliadin Antibodies

Background:The finding of characteristic small intestinal mucosal abnormalities on histologic examination of a biopsy specimen remains the first requirement for the diagnosis of celiac disease. A reliable and noninvasive test would be ideal for the patient's convenience and for reducing health‐care costs. The sensitivity and specificity of anti‐gliadin antibodies (AGA‐immunoglobulin[Ig] G, AGA‐IgA) have been variable; anti‐endomysium IgA (EmA‐IgA) is more helpful. In an earlier study conducted at the authors' institution, celiac disease was present in 19 patients examined from 1992 to 1995. Anti‐endomysium titers were higher than normal in all 19 patients (100%). Total villous atrophy was seen in 14 of 17 biopsy specimens (82%) and subtotal atrophy in 3 (18%). The purpose of the current study was to evaluate further the accuracy of EmA‐IgA in diagnosing celiac disease.Methods:One hundred seven patients were screened for celiac disease between March 1996 and July 1997. The level of EmA‐IgA was measured in all patients, and AGA‐IgG and AGA‐IgA were measured in 104 patients. Forty‐six patients underwent endoscopic biopsy of the small bowel, with measurement of disaccharidase enzymes in 45 patients.Results:Five of 46 patients had celiac disease (three boys and two girls; mean age, 5.3 years; 2‐9.5 years); one also had cystic fibrosis and another had insulin‐dependent diabetes mellitus. All five had marked to complete villous atrophy with crypt hyperplasia and increased serum EmA‐IgA(100% sensitivity). None of the remaining patients had increased EmA‐IgA(100% specificity). Serum levels of AGA‐IgG and AGA‐IgA were increased in all four celiac disease patients (100% sensitivity), but they were also high in patients without celiac disease (38% and 92% specificity, respectively), which compromises their diagnostic value. None of the patients confirmed to have celiac disease had IgA deficiency. Abnormal disaccharidase enzyme activities were documented in all five celiac disease patients: severe generalized deficiency (n = 2), moderately severe generalized deficiency (n = 2), and alactasia with moderate deficiency of theα‐glucosidases (n = 1).Conclusions:This study confirmed the reliability and accuracy of EmA‐IgA in the diagnosis of celiac disease. Small bowel biopsy may be unnecessary in EmA‐positive patients in whom celiac disease is suspected.

Further Studies of Anti‐Endomysium and Anti‐Gliadin Antibodies in Patients with Suspected Celiac Disease

Del Rosario,

Fitzgerald,

Chong

et al. 1998

Comparative Evaluation of Serologic Tests for Celiac Disease: A European Initiative Toward Standardization

Stern

2000

BackgroundSerologic methods have been used widely to test for celiac disease and have gained importance in diagnostic definition and in new epidemiologic findings. However, there is no standardization, and there are no reference protocols and materials.MethodsThe European working group on Serological Screening for Celiac Disease has defined robust noncommercial test protocols for immunoglobulin (Ig)G and IgA gliadin antibodies and for IgA autoantibodies against endomysium and tissue transglutaminase. Standard curves were linear in the decisive range, and intra‐assay variation coefficients were less than 5% to 10%. Calibration was performed with a group reference serum. Joint cutoff limits were used. Seven laboratories took part in the final collaborative study on 252 randomized sera classified by histology (103 pediatric and adult patients with active celiac disease, 89 disease control subjects, and 60 blood donors).ResultsIgA autoantibodies against endomysium and tissue transglutaminase rendered superior sensitivity (90% and 93%, respectively) and specificity (99% and 95%, respectively) over IgA and IgG gliadin antibodies. Tissue transglutaminase antibody testing showed superior receiver operating characteristic performance compared with gliadin antibodies. The κ values for interlaboratory reproducibility showed superiority for IgA endomysium (0.93) in comparison with tissue transglutaminase antibodies (0.83) and gliadin antibodies (0.82 for IgG, 0.62 for IgA).ConclusionsBasic criteria of standardization and quality assessment must be fulfilled by any given test protocol proposed for serologic investigation of celiac disease. The working group has produced robust test protocols and reference materials available for standardization to further improve reliability of serologic testing for celiac disease.

Even Small Amounts of Gluten Cause Relapse in Children With Celiac Disease

Laurin,

Wolving,

Fälth‐Magnusson

2002

BackgroundPreviously, a gluten challenge was customary to establish the diagnosis of celiac disease in children. There are no clear recommendations on how to perform this challenge or what markers to rely on for timing the biopsy after the challenge. The authors' aim was to monitor gluten intake, clinical symptoms, and antibody kinetics to evaluate the influence of gluten exposure during the challenge.MethodsTwenty‐five children under investigation for suspected celiac disease were challenged. One child was excluded because blood samples, food records, or biopsy was lacking. Median age at the postchallenge biopsy was 3.8 (2.7–8.8) years. The families kept daily records of the children's gluten intake and of symptoms that occurred. Blood samples were taken monthly for analysis of antigliadin and endomysium antibodies and total immunoglobulin A (IgA). A third biopsy was performed when clinical symptoms suggested a relapse.ResultsAll 24 children showed deterioration of the mucosa or elevated antibodies during gluten challenge. Median duration of the challenge was 13 (5–51) weeks, and mean gluten intake was 1.7 (0.2–4.3) g/d and 0.1 (0.02–0.26) g/kg daily.ConclusionsGluten intake during the challenge varied widely, and the parents were unable to give their children the recommended amount. Despite the small amounts given, all children showed signs of relapse at a clinical, laboratory, or histologic level. Much smaller amounts of gluten than previously suggested seem sufficient to cause relapse during gluten challenge in children.