Celiac disease

Celiac disease (CD) is a lifelong, gastrointestinal disorder caused by intolerance to gluten, a complex mixture of proteins found in wheat, barley and rye. Once the disease has developed it can only be treated by a lifelong gluten-free diet.

Celiac disease is an autoimmune disease caused by aberrant T-cell mediated immune responses to the gluten proteins. As a by-product of the T-cell response to modified gluten, patients usually also produce antibodies to both tissue transglutaminase and modified gluten. As these antibodies are secondary to the T-cell response to gluten, their presence is highly predictive for Celiac disease. In addition, the disease is linked to HLA DQ2/DQ8 and has been shown to be related with type I diabetes, Down’s syndrome, Turners syndrome and autoimmune thyroid disease. The pathology of the disease is caused by intestinal inflammation leading to the destruction and truncation of the villi. The decrease in intestinal surface area and dysfunctional villi results in malnutrition among other clinical effects. Early diagnosis of asymptomatically CD is justified as serious complications may develop such as osteoporosis and malignancies.


Celiac disease (CD) is a serious, lifelong, gastrointestinal dis­order that can cause a wide spectrum of clinical symptoms of diarrhoea, abdominal distension, weight loss, malnutrition and skin disorders (Dermatitis herpetiformis) due to perma­nent intolerance to gluten. Other manifestations include iron deficiency with or without anaemia, recurrent abdominal pain, chronic fatigue, and reduced bone mineral density.


Once considered a gastrointestinal disease of childhood affecting mainly whites, celiac disease is now recognized as a systemic disease that may affect persons of any age and many races and ethnic groups. It is generally accepted that the prevalence of celiac disease is 0.5 to 1% in the Western Hemisphere and a similar occurrence is likely in North Africa, the Middle East, India and parts of China. This makes celiac disease one of the most prevalent food induced disorders known. Most persons with Celiac disease are unaware of that they have the disease. Serologic screening studies have shown that only a small proportion of cases of celiac disease are clinically recognized (21% in a recent European study).


The golden standard for diagnosis of Celiac disease is histology on small intestine biopsies. Celiac disease is seen as mucosal injuries, villous atrophy with crypt hyperplasia. The injuries are categorized according to the Marsh classification (0-4). However, as this procedure is associated with significant morbidity especially in children, non-invasive serological tests have been developed, such as determination of autoantibodies against gliadin/deaminated gliadin and tissue transglutaminase (tTG).

Based on these tests, a test algorithm and test consensus has been created which, however, may differ between countries. Usually the algorithm contains anti-tTG IgA together with determination of total IgA, as a significant number of celiac patients are deficient in IgA. A common adjunct test is the IgG anti-deamidated gliadin (DG) which has been shown to be both specific and sensitive for celiac disease and the 2012 Clinical Guideline from  ESPHGHAN and NASPGHAN opened up for use of deamidated gliadin as a complement to tTg, especially in children.

Euro Diagnostica has recently introduced a highly sensitive anti-DG test based on unique synthetic deamidated gliadin peptides containing a well-defined T cell stimulatory toxic epitope, which is known to be involved in celiac disease. This assay has been shown to possess a very high sensitivity and specificity and is well suited as an adjunct test to the IgA anti-tTG providing valuable additional information.

The majority of the patients (90-95%) carry the HLA-DQ heterodimer encoded by DQA1*05/DQB1*02 (denoted DQ2 serologically) either in cis or in trans, while the remaining patients (10%) carry either part of the DQ2 heterodimer or DQA1*03-DQB1*03:02 (denoted DQ8 serologically).

Activation of the “gluten”-specific CD4+ mucosal T cells is likely to be most pronounced in those individuals who are homozygous for HLA-DQ2, or in those who are heterozygous such that they have a double dose of the HLA-DQB1*02 allele. Carrying two copies of DQB1*02 allele is associated with an even greater risk for CD, but does not predict an earlier age of onset of disease or disease severity. This suggests that the assessment of copy number of the DQB1*02 allele could permit stratification of the risk.

Because of the strong association between Coeliac Disease and the HLA genotypes previously described, an exhaustive system for the detection of genetic susceptibility to coeliac disease must be able to provide the following information:

1. HLA alleles coding for DQ2 and DQ8 heterodimers

2. All HLA genotypes responsible for coding DQ2 e DQ8 heterodimers

3. Identification of all risk classes predisposing to coeliac disease

Relevant Literature

  1. Tjon JM, van Bergen J, Koning F. Immunogenetics. 2010 Oct;62(10):641-51
  2. Sollid LM, Qiao SW, Anderson RP, Gianfrani C, Koning F. Immunogenetics. 2012 Jun;64(6):455-60
  3. Vader W, de Ru A, van der Wal Y, Kooy Y, Benckhuijsen W, Mearin L, Drijfhout JW, van Veelen P, and Koning F. J. Exp. Med. 2002 Mar 4;195(5):643-9
  4. Husby S, Koletzko S, Korponay-Szabó IR, Mearin ML, Phillips A, Shamir R, Troncone R, Giersiepen K, Branski D, Catassi C, Lelgeman M, Mäki M, Ribes-Koninckx C, Ventura A, Zimmer KP. J Pediatr Gastroenterol Nutr. 2012 Jan;54(1):136-60