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

Muhammed Hadithi, B Mary E von Blomberg, J Bart A Crusius, Elisabeth Bloemena, Pieter J Kostense, Jos W R Meijer, Chris J J Mulder, Coen D A Stehouwer, Amado S Peña

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173 Citations (Scopus)


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.

Original languageEnglish
Pages (from-to)294-302
Number of pages9
JournalAnnals of Internal Medicine
Issue number5
Publication statusPublished - 4 Sept 2007


  • Adult
  • Autoantibodies/blood
  • Biopsy
  • Celiac Disease/diagnosis
  • 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

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