Coeliac Disease: background and biochemical aspects

Coeliac Disease has to be considered a main food related affliction, with life long consequences for the people having the disease. Coeliac Disease patients suffer from adverse effects that can be related to specific gluten peptide sequences that trigger a sequence of immune related reactions leading to damage of the intestine and related malabsorption symptoms. Recently, detailed information has come available on peptide sequences that are toxic for Coeliac Disease patients. This information is discussed in relation to prevention of the disease and the development of safe cereals for Coeliac Disease patients.     

Antibodies in the Diagnosis of Coeliac Disease: A Biopsy-Controlled,International, Multicentre Study of 376 Children with Coeliac Disease and 695 Controls

Diagnosis of coeliac disease (CD) relies on a combination of clinical, genetic, serological and duodenal morphological findings. The ESPGHAN suggested that biopsy may not be necessary in all cases. New guidelines include omission of biopsy if the concentration of CD-specific antibodies exceeds 10 times the upper limit of normal (10 ULN) and other criteria are met. We analysed the 10 ULN criterion and investigated multiple antibody-assays. Serum was collected from 1071 children with duodenal biopsy (376 CD patients, 695 disease-controls). IgA-antibodies to tissue transglutaminase (IgA-aTTG), IgG-antibodies to deamidated gliadin peptides (IgG-aDGL) and IgA-endomysium antibodies (IgA-EMA) were measured centrally. We considered 3 outcomes for antibody test procedures utilizing IgA-aTTG and/or IgG-aDGL: positive (≥10 ULN, recommend gluten-free diet), negative (<1 ULN, no gluten-free diet) or unclear (perform biopsy). Positive (PPV) and negative (NPV) predictive values were based on clear test results. We required that they and their lower confidence bounds (LCB) be simultaneously very high (LCB >90% and PPV/NPV >95%). These stringent conditions were met for appropriate antibody-procedures over a prevalence range of 9–57%. By combining IgG-aDGL with IgA-aTTG, one could do without assaying total IgA. The PPV of IgG-aDGL was estimated to be extremely high, although more studies are necessary to narrow down the LCB. The proportion of patients requiring a biopsy was <11%. The procedures were either equivalent or even better in children <2 years compared to older children. All 310 of the IgA-aTTG positive children were also IgA-EMA positive. Antibody-assays could render biopsies unnecessary in most children, if experienced paediatric gastroenterologists evaluate the case. This suggestion only applies to the kits used here and should be verified for other available assays. Confirming IgA-aTTG positivity (≥10 ULN) by EMA-testing is unnecessary if performed on the same blood sample. Prospective studies are needed.     

Fingerprint Changes in Coeliac Disease

Study of the fingerprints of 73 patients with coeliac disease, taken carefully, showed changes varying between moderate epidermal ridge atrophy and actual loss of fingerprint patterns. Of the patients 63 had these abnormalities, compared with 3 out of 485 controls. A high degree of correlation existed between ridge atrophy and changes in the clinical state of patients with coeliac disease.     

Follow up Study of Coeliac Disease

In 9 out of 10 adults in whom a diagnosis of coeliac disease had been made in childhood, the diagnosis was confirmed by the finding of a flat intestinal mucosa. None showed abnormal physical signs, but three had a haemoglobin concentration below 10 g./100 ml. and all those not receiving folic acid supplements showed low serum folate levels. Five had moderate to severe symptoms at the time of investigation, but none was receiving treatment with a gluten-free diet.Periodic investigation of these patients may be necessary throughout life, and if they are found to have malnutrition they should be treated with a gluten-free diet.     

Immune Response to Gluten in Adult Coeliac Disease

Cultures of mesenteric node lymphocytes obtained from two adult coeliac disease patients were stimulated by gluten fraction III. No stimulation was observed in cultures of axillary node lymphocytes from one of these patients, of mesenteric node lymphocytes from the two patients with other diseases or of peripheral blood lymphocytes from adult coeliacs and normal subjects. Peripheral blood lymphocytes of two of the six adult coeliac patients responded poorly to phytohaemagglutin alone, but this was probably owing to technical factors. In a further six adult coeliacs skin tests to gluten fraction III were negative. It is suggested that delayed hypersensitivity to gluten is likely to have a secondary pathogenic role in adult coeliac disease.     

Incidence of Coeliac Disease in the West of Ireland

During an 11-year period the incidence of coeliac disease presenting in children in the West of Ireland has been found to be 1 in 597. When allowance is made for presentation of the disease in adult life the incidence may be as high as 1 in 303. These figures are much higher than those reported for Britain.     

Fingerprints in Patients with Coeliac Disease and their Relatives

The incidence of fingerprint pattern abnormality in 53 patients with coeliac disease and 82 of their relatives was not greater than that found in 58 control subjects. This finding contradicts an earlier report that most patients with coeliac disease had abnormal fingerprints.