Accuracy of serologic tests and HLA-DQ typing for diagnosing celiac disease

Ann Intern Med. 2007 Sep 4;147(5):294-302. doi: 10.7326/0003-4819-147-5-200709040-00003.

Abstract

Background: Estimates of the diagnostic performance of serologic testing and HLA-DQ typing for detecting celiac disease have mainly come from case-control studies.

Objective: To define the performance of serologic testing and HLA-DQ typing prospectively.

Design: Prospective cohort study.

Setting: University hospital.

Patients: Patients referred for small-bowel biopsy for the diagnosis of celiac disease.

Interventions: Celiac serologic testing (antigliadin antibodies [AGA], antitransglutaminase antibodies [TGA], and antiendomysium antibodies [EMA]) and HLA-DQ typing.

Measurements: Diagnostic performance of serologic testing and HLA-DQ typing compared with a reference standard of abnormal histologic findings and clinical resolution after a gluten-free diet.

Results: Sixteen of 463 participants had celiac disease (prevalence, 3.46% [95% CI, 1.99% to 5.55%]). A positive result on both TGA and EMA testing had a sensitivity of 81% (CI, 54% to 95.9%), specificity of 99.3% (CI, 98.0% to 99.9%), and negative predictive value of 99.3% (CI, 98.0% to 99.9%). Testing positive for either HLA-DQ type maximized sensitivity (100% [CI, 79% to 100%]) and negative predictive value (100% [CI, 98.6% to 100%]), whereas testing negative for both minimized the negative likelihood ratio (0.00 [CI, 0.00 to 0.40]) and posttest probability (0% [CI, 0% to 1.4%]). The addition of HLA-DQ typing to TGA and EMA testing, and the addition of serologic testing to HLA-DQ typing, did not change test performance compared with either testing strategy alone.

Limitation: Few cases of celiac disease precluded meaningful comparisons of testing strategies.

Conclusions: In a patient population referred for symptoms and signs of celiac disease with a prevalence of celiac disease of 3.46%, TGA and EMA testing were the most sensitive serum antibody tests and a negative HLA-DQ type excluded the diagnosis. However, the addition of HLA-DQ typing to TGA and EMA testing, and the addition of serologic testing to HLA-DQ typing, provided the same measures of test performance as either testing strategy alone.

MeSH terms

  • Adult
  • Autoantibodies / blood
  • Biopsy
  • Celiac Disease / diagnosis*
  • Celiac Disease / pathology
  • Enzyme-Linked Immunosorbent Assay
  • Female
  • Fluorescent Antibody Technique, Indirect
  • Genotype
  • Gliadin / immunology
  • Glycoside Hydrolases / immunology
  • HLA-DQ Antigens / genetics*
  • Humans
  • Immunologic Tests*
  • Intestine, Small / pathology
  • Male
  • Middle Aged
  • Prospective Studies
  • Transglutaminases / immunology

Substances

  • Autoantibodies
  • HLA-DQ Antigens
  • Gliadin
  • Transglutaminases
  • Glycoside Hydrolases
  • endo-alpha-sialidase