Serological Screening Tests

Serological tests are helpful in detecting celiac disease in individuals with nongastrointestinal symptoms, and high-risk groups who may or may not have signs of disease. The clinicians often use the serological results to triage those who need small bowel biopsy. The high-risk groups include first-degree relatives of confirmed cases of celiac disease, those with type 1 diabetes mellitus, Down's syndrome, Turner's syndrome and unexplained dental enamel deficits, and children with unexplained short stature. Serological tests are also used to monitor progress after diagnosis as well as in prevalence studies in unselected populations. The ser-ological tests utilized in current clinical practice include the endomysial antibody, tissue transgluta-minase antibody, and the anti-gliadin antibodies (IgA and IgG).

An enzyme-linked immunosorbent assay (ELISA) for both the IgA and IgG subclass of antibodies to gliadin has been used for the diagnosis of celiac disease. Their role in diagnosis is limited because of moderate sensitivity and specificity. The antiglia-din antibodies are found in intestinal secretions as well as in serum of patients with untreated celiac disease. However, these antibodies are also found in a variety of autoimmune disorders including rheumatoid arthritis, Sjogren's syndrome, sarcoidosis, inflammatory bowel disease, and cows' milk protein intolerance. IgA antigliadin antibodies have sensitivity of 75-90% and specificity of 82-95%. The IgG antigliadin antibodies range in sensitivity from 69% to 85% and have specificity of 73-90%; they are useful in the diagnosis of celiac patients with IgA deficiency. Other than this use gliadin antibodies have fallen from favor as a screening test for celiac disease (National Institute of Health consensus panel).

The IgA antiendomysial antibody (EMA) assay is directed against the connective tissue protein found in the collagenous matrix of human and monkey tissue. This antibody is found in association with celiac sprue. The test is based on immunofluores-cence techniques using monkey esophagus or human umbilical cord as a substrate. Although quite sensitive (85-98%) and specific (97-100%), the test has several limitations including false-negative results in 23% of patients with celiac disease who have selective IgA deficiency. Other factors that have an impact on the sensitivity and specificity of this test include laboratory variations and disease severity. In a study of 101 patients with untreated celiac disease the sensitivity of the endomysial antibody in those with total villous atrophy was excellent (100%), but decreased remarkably (31%) in patients with partial villous atrophy. The endomysial antibody performed by the indirect immuno-flourescent assay (IFA) technique is technically challenging and is being replaced by the tissue transglutaminase antibody test.

Tissue transglutaminase (tTG) is a cytosolic protein released by damaged epithelial cells. This is the autoantigen recognized by the endomysial antibody indirect immunofluorescence assay in patients with celiac disease. The advantages of this test are that it is performed using ELISA techniques, which makes it easier to perform, is widely available, and less costly. It eliminates the use of monkey esophagus as well as the subjective interpretation of immuno-fluorescence analysis of the endomysial antibody test. Though the tTG test is comparable to EMA in sensitivity, there is loss of specificity in patients with autoimmune disorders, hence it is important to confirm the diagnosis with small intestine biopsy.

In some patients biopsies are taken during an endoscopy that has been performed for another reason. In these patients serological tests can be useful to help confirm the diagnosis if there is some uncertainty with an equivocal biopsy, while negative serology in this circumstance may indicate another cause. Celiac disease may occur in the absence of antibodies however.

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