IgA Antitissue Transglutaminase and IgA Antiendomysial Antibodies Help Diagnose Celiac Disease

Laurie Barclay, MD

May 10, 2010

May 10, 2010 — Immunoglobulin A (IgA) antitissue transglutaminase antibodies and IgA antiendomysial antibodies are highly sensitive and specific in diagnosing celiac disease, according to the results of a systematic review reported in the May 5 issue of the Journal of the American Medical Association.

"The symptoms and consequences of celiac disease usually resolve with a lifelong gluten-free diet," write Daniëlle A. W. M. van der Windt, PhD, from Arthritis Research UK National Primary Care Centre at Keele University in Staffordshire, and colleagues. "However, clinical presentation is variable and most patients presenting with abdominal symptoms in primary care will not have celiac disease and unnecessary diagnostic testing should be avoided."

The goal of this review was to synthesize available information on the performance of diagnostic tests for detecting celiac disease in adults who presented with abdominal symptoms to primary care or similar settings. The reviewers searched MEDLINE from January 1966 through December 2009 and EMBASE from January 1947 through December 2009. In addition, they manually searched bibliographies for additional pertinent studies.

Inclusion criteria were cohort or nested case-control design, participants including adults with nonacute abdominal symptoms, study population with prevalence of celiac disease of 15% or less, and use of gastrointestinal tract symptoms or serum antibody tests for diagnosis. The Quality Assessment of Diagnostic Accuracy Studies tool allowed evaluation of study quality.

Two reviewers independently extracted data, and sensitivities and specificities were computed for each study. If there was clinical and statistical homogeneity, pooled estimates were calculated by use of bivariate analysis.

There were 16 studies meeting inclusion criteria, enrolling a total of 6085 patients. Diagnostic performance of abdominal symptoms varied widely (eg, with a sensitivity of diarrhea ranging from 0.27 to 0.86 and a specificity from 0.21 to 0.86).

For IgA antiendomysial antibodies (8 studies), pooled estimates were 0.90 (95% confidence interval [CI], 0.80 - 0.95) for sensitivity and 0.99 (95% CI, 0.98 - 1.00) for specificity, yielding a positive likelihood ratio (LR) of 171 and a negative LR of 0.11. For IgA antitissue transglutaminase antibodies (7 studies), pooled estimates were 0.89 (95% CI, 0.82 - 0.94) and 0.98 (95% CI, 0.95 - 0.99), respectively, resulting in a positive LR of 37.7 and a negative LR of 0.11. Results were variable for IgA and IgG antigliadin antibodies, particularly for sensitivity, which ranged from 0.46 to 0.87 and from 0.25 to 0.93, respectively.

Although specificity was good (≥ 0.94) in 1 recent study using diamidated gliadin peptides, evidence is limited in this target population.

"Among adult patients presenting with abdominal symptoms in primary care or other unselected populations, IgA antitissue transglutaminase antibodies and IgA antiendomysial antibodies have high sensitivity and specificity for diagnosing celiac disease," the review authors write.

Limitations of this review include those inherent in the included studies and limited power for subgroup analyses. For nested case-control designs, risk is increased for selection bias and clinical review bias.

"In adult patients presenting with chronic abdominal symptoms, symptoms alone are insufficient for diagnosing celiac disease," the review authors conclude. "The IgAtTG [antitissue transglutaminase] and EmA [antiendomysial] tests show good performance, but the evidence in primary care populations is limited. Further research should investigate the performance of a diagnostic algorithm, using sequential serological testing in patients with chronic or refractory abdominal symptoms in primary care."

The Netherlands Organization for Health Research and Development supported this review. The review authors have disclosed no relevant financial relationships.

JAMA. 2010;303:1738-1746. Abstract

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