Widodo Judarwanto MD, Indonesia Celiac Clinic

Celiac disease is a hereditary intolerance to gluten, a protein found in wheats and, to a lesser extent in barley, rye, and oats. While gluten intolerance is permanent, symptoms can be alleviated by avoiding all gluten from one’s diet. Inflammation occurs when gliadin, a peptide derivative of gluten, found in gluten-containing foods is ingested and presented to T cells. Inflammation causes damage to mucosal tissue of the small intestine, especially the villi that absorb nutrients, which results in malabsoption of food. Celiac disease affects as many as 1 in 300 people in Italy and southwestern Ireland, but is extremely rare in Africa, Japan, and China.

According to a multicenter study in 2003, there is a 1 in 133 chance that people with no risk factors or family history in the U.S. have celiac disease. Additionally, a persons risk increases to a 1 in 22 chance if they have a first-degree relative with celiac disease and a 1 in 39 chance if they have a second-degree relative Around 60,000 Americans are diagnosed with celiac disease annually and a total of over 2 million have the disease, making it perhaps the most common genetic disorder in the United States. Celiac disease can occur at any age, and females are more commonly affected than males. Of females presenting during their fertile years, the male to female ratio is almost 3 to 1

Genetic Risk Factors
Celiac disease is strongly associated with the human leukocyte antigen (HLA) DQ2 and DQ8 haplotypes. HLA genes are part of the major histocompatibility complex (MHC). The function of MHC molecules is to bind peptide fragments derived from pathogens and display them on the cell surface for recognition by T cells. Many proteins involved in antigen processing and presentation are encoded by genes within the MHC

The HLA-DQ2 allele is identified in 90 to 95% of patients with celiac disease, and HLA-DQ8 is identified in most of the remaining patients. Because these alleles occur in 30 to 40% of the general population (with HLA-DQ2 more common than HLA-DQ8), the absence of these alleles is important for its high negative predictive value. Thus, the presence or absence of HLA-DQ2 and HLA-DQ8 is important for determining which family members should be screened with serologic testing and is useful for ruling out the disease in patients already on a gluten-free diet or for patients in whom the diagnosis is unclear.

Symptoms of celiac disease are caused by a glutamine and proline rich 33-mer peptide found in gluten that initiates the inflammatory response when bound to these HLA haplotypes (Shan, Lu et al, 2002). The primary HLA association in most patients with celiac disease is with DQ2 (DQA*05/DQB1*02) and in a minority of patients with DQ8 (DQA1*03/DQB1*0302).

Approximately 97% of individuals with celiac disease have the HLA-D2Q or HLA-DQ8, compared to 40% of the general population (NIH, 2006). The x-ray crystal structure of the soluble domain of HLA-DQ2 was observed bound to the deaminated gluten epitope alpha-I-gliadin. The HLA association in celiac disease can be explained by a superior ability of DQ2 to bind the repertoire of proline-rich gluten peptides that have survived gastrointestinal digestion and that have been deaminated by tissue transglutaminase

Celiac disease is diagnosed in about 10% of first degree relatives of an individual with celiac disease. Although hereditary factors play a significant role, genetic factors alone do not explain the development of the disease because the disease is concordant in only 60% to 70% of identical twins. All people with HLA DQ2 and DQ8 do not develop into disease, and others without those alleles can develop celiac disease, so more genes may be involved. Additional factors such as hormones and infectious agents may also be involved in linking the ingestion of gluten with a chronic inflammatory reaction in the intestine in genetically predisposed individuals


  • Johnson TC, Diamond B, Memeo L, et al. Relationship of HLA-DQ8 and severity of celiac disease: comparison of New York and Parisian cohorts. Clin Gastroenterol Hepatol 2004;2:888-894.
  • Kaukinen K, Partanen J, Mäki M, Collin P. HLA-DQ typing in the diagnosis of celiac disease. Am J Gastroenterol 2002;97:695-699.



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