Serologic panel Of the commercially available serologic tests that aid in the diagnosis of celiac disease, no one test is ideal. Using multiple serologies increases the diagnostic yield. Therefore, in the United States, screening in patients with possible celiac disease should consist of a panel of the following serologic tests:
Selective IgA deficiency (SIgA deficiency) SIgA deficiency occurs 10 to 15 times more commonly among people with celiac disease compared to the general population [19]. Patients with SIgA deficiency will lack IgA antibodies including endomysial antibody, tTG and IgA AGA. To detect celiac disease in patients with SIgA deficiency an IgG antibody, typically IgG AGA, needs to be performed together with total IgA level. Alternatively, one may screen with IgG anti- EMA or IgG anti-tTG, though these are not widely available. Typically the patient with celiac disease and SIgA deficiency will have a positive IgG AGA and absent total IgA level. This combination should prompt a biopsy, whereas an isolated positive IgG AGA would usually not. Lack of concordance of endomysial antibody and anti-tTG The discovery that the enzyme tissue transglutaminase (tTG) was the autoantigen for the endomysial antibody [20] prompted the development of ELISA testing for tTG. This allowed automation of the test for the detection of anti-tTG. The measurement of the EMA required a cumbersome, observer dependant immunoflourescence technique. As a result many laboratories have replaced the endomysial antibody with the anti-tTG test. However the test does not measure the same thing and there are differences in preparation of the antigen (tTG), either tTG from guinea pig liver or human tTG, preparation of the kits and cutoff values for each patient population. In addition there may be other antigens, apart from tTG , for the EMA [21]. The EMA is certainly the gold standard in the serologic diagnosis of celiac disease, for it is virtually 100% specific. However multiple cases have demonstrated that patients may be positive for one (either EMA or anti-tTG) and negative for the other, i.e. they lack 100% concordance [22-25]. As a result reliance on the anti-tTG as a single test will underestimate the presence of celiac disease and both the EMA and the anti-tTG should be performed. Seronegative celiac disease Both the anti-tTG and the EMA titers correlate with the severity of villous atrophy [26-29]. As a result in the presence of partial villous atrophy either antibody may be negative. In addition the mode of presentation of the celiac disease, i.e. presence of silent or subclinical celiac disease may be associated with a negative EMA [30]. Clinically seronegative celiac disease is similar to sero-positive celiac disease [23, 28] In view of the possibility of the presence of celiac disease in the absence of a positive anti-tTG or endomysial antibody the presence of a positive IgA AGA should prompt a biopsy [13]. Several studies have demonstrated that reliance on either anti-tTG or endomysial antibody as a single test will underestimate the prevalence of celiac disease [23, 25, 31, 32]. Causes of false positive celiac serologic tests The endomysial antibody test is virtually 100% specific for celiac disease. However anti-tTG has been reported to be positive in the presence of liver disease, especially cirrhosis [33], diabetes [34, 35] and severe heart failure [36], as well as arthritis [37] and various autoimmune disorders [38]. The use of human tTG as the antigen in the test kit adds some greater specificity. Antigliadin antibodies may be present in inflammatory bowel disease [39], collagen vascular disease [40], and in many healthy people as well [41]. Positive serologic tests in the presence of a normal biopsy This situation occasionally arises. The presence of a positive EMA with a normal biopsy indicates either the presence of celiac disease that was not detected in the biopsy, either because of too few pieces being taken or misinterpretation. The biopsy should be reviewed by an expert gastrointestinal pathologist. If it is considered to be truly a normal biopsy the patient may well have latent celiac disease and will probably develop the disease at a later date. Genetic testing for celiac disease Celiac disease is a multigenic disorder associated with HLA-DQ2 (DQA1*05/DQB1*02) or DQ8 (DQA1*0301/DQB1*0302). HLA DQ2 is expressed in the majority (>90%) of those with celiac disease and DQ8 in about 8%. The expression of these HLA-DQ2 or DQ8 molecules is necessary but not sufficient to develop celiac disease and accounts for only about 50% of the genetic component of the disease. Studies in sibling (sib recurrence risk for celiac disease of 10%) [42] and of identical twins (concordance of 70%) [43] suggest that the contribution of HLA genes in celiac disease is less than 50%. The determination of the presence of HLA DQ2 or DQ8 is now available commercially. The role in the diagnosis of celiac disease is however limited because of the low specificity of the test for celiac disease. These HLA types are present in about 30% of the normal population. Their absence is useful in excluding celiac disease. The role in assessment of the presence of HLA DQ2 or is: 1. In the presence of an equivocal biopsy, 2. When someone is already on the diet, 3. To determine which family members should be screened for celiac disease.
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