Abstract
Source: Maki M, Mustalahti K, Kokkonen J, et al. Prevalence of celiac disease among children in Finland. N Engl J Med. 2003;348:2517–2524.Using the most sensitive and specific serological tests available (detecting serum endomysial and tissue transglutaminase antibodies along with human lymphocyte antigen [HLA] typing), these Finnish investigators tested the hypothesis that assays for serum autoantibodies can be used to detect untreated celiac disease (CD), and that positive findings correlate with specific HLA haplotypes. Serum samples that were collected and frozen in 1994 for a study of risk factors for type I diabetes were re-studied. Samples from 3,654 asymptomatic students (age range, 7 to 16 years when the samples were taken in 1994) were screened in 2001 for endomysial and tissue transglutaminase antibodies. Of those 56 (1.5%) had positive serological tests. Of those, who had positive tests, 10 (18%) had become symptomatic and were diagnosed before the screening in 2001. Of the 36 asymptomatic children who underwent further testing, 27 (75%) had evidence of CD on biopsy resulting in a biopsy-proven disease prevalence of 1 in 99 school children. All but 2 of the antibody-positive subjects had either the HLA-DQ8 or the HLA-DQ2 haplotype. It was suggested that the 25% of children without evidence of disease but who have positive serologic tests will eventually show evidence of disease. The prevalence of the combination of antibody positivity and an HLA haplotype associated with CD was 1 in 67.The authors conclude that the presence of serum tissue transglutaminase and endomysial autoantibodies is predictive of small-bowel abnormalities indicative of CD. There was a good correlation between autoantibody positivity and specific HLA haplotypes.Another paper and editorial in the same issue provides a brief but very enlightening discussion of the basic pathophysiology of CD and its genetic associations. 1,2 CD represents a unique model of autoimmune disease. The enzyme tissue transglutaminase, which is expressed in the subepithelial layer of the intestine, has been identified as the target of the endomysial autoantibody. This provides a potential explanation for how and why tissue damage occurs from gluten. There is a close genetic association with HLA-DQ2 in 90–95% of cases and to HLA DQ8 in 5–10% of cases; an identifiable triggering environmental stimulus (gluten); and a highly specific humoral autoimmune response (autoantibodies against tissue transglutaminase)—all of which provide the rationale for the treatment of the disease, which is complete avoidance of gluten.2 In view of increasing evidence that there are a significant number of undiagnosed cases, the editorial raises the issue of screening for this disease and concludes that “the best epidemiologic approach to the diagnosis of CD seems to be a systematic process of case-finding in which patients with symptoms or conditions, both typical and atypical, known to be associated with the disease are targeted.”The questions that most pediatricians want answered are: who should be tested? When, and how? Anti-gluten antibodies are useless and should not be ordered. They have been supplanted by the anti-endomysial IgG and IgA antibodies and IgA antibodies to tissue transglutaminase. (A total serum IgA should accompany these tests since those that lack IgA antibodies would, even if they had CD, lack both IgA endomysial and tissue transglutaminase IgA antibodies.) The use of HLA testing seems best reserved for confusing or difficult cases. Small bowel biopsy—at least once—remains a part of the diagnostic work-up for now, although it has been suggested that it may not be necessary for all cases.3 A high index of suspicion should warrant close continued observation and, if concerns persist, serological testing.Alert your labs to get spruced up for more serologic testing for celiac disease.
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