Gluten consists of various proteins found in grains such as wheat, barley, and rye. In celiac disease gluten causes an abnormal immunological reaction which results in inflammation and mucosal damage in the small bowel. The autoimmune disorder mostly manifests between 1 to 5 years of age. The only effective therapy is a lifelong diet strictly avoiding gluten containing foods. For diagnosis, physicians order a blood test for autoantibodies against tissue-transglutaminase (tTGA-IgA). These autoantibodies are proteins produced by immune cells and directed towards own tissue in the gut. Increased tTGA-IgA values in blood make the diagnosis of celiac disease already very likely. For confirmation of mucosal lesions, an upper endoscopy with tissue sampling (biopsies) from the upper intestine is required. In children this is performed under anesthesia and implies a major burden.
In recent years the European Society of Paediatric Gastroenterology, Hepatology and Nutrition (ESPGHAN) proposed that in children with very high tTGA levels in blood (10-fold or more the upper limit of normal), intestinal biopsies can be omitted if certain additional criteria are fulfilled. These include the presence of symptoms suggesting celiac disease, the presence of other auto-antibodies (EMA-IgA), and genetic risk markers (HLA-DQ2/DQ8). But there were major doubts whether omitting biopsies would result in false diagnoses and unnecessary therapies. To evaluate the criteria for the non-biopsy approach in clinical practice, Prof. Sibylle Koletzko, head of Paediatric Gastroenterology at Dr. von Hauner Children’s Hospital, and her co-worker Dr. Katharina Werkstetter initiated in November 2011 the large study ProCeDE. Pediatricians from 33 children’s hospitals in 21 countries prospectively collected data, blood and biopsy material from over 700 children and adolescents which tested positive for celiac specific autoantibodies.
The ProCeDE study clearly showed that the combination of very high tTGA-IgA and positive EMA-IgA in a 2nd blood sample allows a secure diagnosis of celiac disease in symptomatic children. The reliability was independent of country and the type of serological tTGA-IgA test used. At the local sites, 10 different and in the central control laboratory 8 different tTGA tests were applied. All patients fulfilling the criteria (399 of 707) tested positive for the genetic risk markers. Therefore this test can be omitted for the non-biopsy approach.
Confirmation of autoantibodies in a 2nd blood sample should always be performed if biopsies are not taken to exclude potential errors due to rarely occurring but possible mix ups of blood samples. If tTGA-IgA levels are abnormally increased but lower than 10-fold the normal value, it is highly recommended to continue performing endoscopy with biopsies to confirm the diagnosis. Testing for additional antibodies, e.g. against deaminated gliadin peptides (DGP) does not reduce the number of children requiring biopsies for celiac diagnosis, and therefore is not beneficial for the patient.
“The results are reassuring and provide strong support for the non-biopsy approach suggested by the European paediatric gastroenterology society” says Prof. Sibylle Koletzko. This avoids the burden, risks and costs of endoscopy and anesthesia for many children with celiac disease worldwide. Expensive genetic analyses are not required for accurate diagnosis.” Because of the complexity and possible pitfalls in the interpretations of test results, special knowledge is required. Therefore Prof. Koletzko recommends that parents should involve a pediatric gastroenterologist or pediatrician knowledgeable in celiac disease to confirm the diagnosis (with or without biopsies). Whether a non-biopsy approach can be also used in children without any symptoms, or in adults, needs to be clarified in further studies.