Q:

What serologic assays are available to screen for celiac disease?

A:

Celiac disease and related disorders are categorized as the "gluten-sensitive enteropathies." Gluten-sensitive enteropathy is characterized as a non-allergic hypersensitivity to gluten or storage proteins found in wheat rye, barley, oats, and corn. This hypersensitivity causes intestinal villous atrophy (flattening) and its physiologic consequences: malabsorption and malnutrition.

In celiac disease, the pathology is primarily confined to the digestive tract. Classic symptoms include: diarrhea, weight loss, abdominal pain and distention, fatigue, oral ulceration, bleeding tendency, proximal myopathy, and bone and joint pain. Short stature, delayed puberty, arthritis, or arthralgia may also result from the untreated disease.

Celiac disease is especially difficult to diagnose. Final diagnosis frequently necessitates small bowel biopsies. However, the newer serologic tests for antibodies to smooth muscle endomysium and tissue transglutaminase, reticulin, and sometimes gliadin are proving useful in diagnosing these conditions.

IgA class endomysial antibodies are seen in gluten-sensitive enteropathies. Endomysium is the connective tissue stroma covering individual muscle fibers or cells. IgA class endomysial antibodies react with the endomysial component of smooth muscle layers of esophagus tissue sections.

Almost 100% of patients with active celiac disease will demonstrate IgA antibodies. These antibodies generally decrease or become negative in patients on gluten-free diets and will usually reappear upon gluten challenge. Serum tests for IgA class endomysial antibodies in conjunction with tests for antibodies to reticulin or gliadin enable the serologic detection of virtually all cases of celiac disease.

Tissue Transglutaminase Antibody, IgA

Recently, the endomysial antigen has been identified as the protein cross-linking enzyme known as tissue transglutaminase. IgA anti-tissue transglutaminase is 85% sensitive and 97% specific for celiac disease.

The particular mechanism by which tissue transglutaminase (tTG) causes damage in celiac disease is unknown, but is thought to be immune mediated. Gliadin in grains triggers the production of serum IgA tissue autoantibodies.

Because of the high sensitivity, tissue transglutaminase antibodies may prove useful for the screening of celiac disease in patients considered to be at low or medium risk for celiac disease. To avoid duodenal biopsies in patients without celiac disease, the specificity of the screening procedure may be increased by confirming with antiendomysial antibodies by immunofluorescence.

IgA anti-tissue transglutaminase, in high titers, is associated with celiac disease. Low titers are not considered to be disease specific.

Test results alone are not diagnostic. Results should be used in conjunction with other clinical findings to make a diagnosis of a gluten-sensitive enteropathy.

Reticulin Antibody, IgA

IgA class reticulin antibodies react with connective tissue fibers and are most easily demonstrated on rat or mouse kidney substrates and also rat or mouse stomach.

IgA class reticulin antibodies are found in 60% of celiac disease patients. IgG class reticulin antibodies are occasionally found in other disease states, especially bullous dermatoses and in some normal subjects.

Gliadin Antibodies, IgA and IgG

The gliadin antibodies (GA) are IgG and IgA antibodies against a group of proteins found in the gluten of wheat and rye grains. The ELISA test for GA is a reliable screening tool for the evaluation of asymptomatic celiac disease in pre-pubertal children with short stature.

GA are useful in screening populations at risk for celiac disease and other gluten- sensitive enteropathies, and in monitoring patient compliance to a gluten-free diet. In celiac disease, IgG antibodies are more sensitive than IgA antibodies, but IgA antibodies are more specific than IgG antibodies. The level of IgA antibodies decreases with a gluten-free diet. IgA and IgG antibodies rise significantly during gluten challenge, sometimes several months before clinical relapse.