Accuracy of Serologic Tests and HLA-DQ Typing for Diagnosing Celiac Disease

  1. Muhammed Hadithi, MD;
  2. B. Mary E. von Blomberg, PhD;
  3. J. Bart A. Crusius, PhD;
  4. Elisabeth Bloemena, MD, PhD;
  5. Pieter J. Kostense, PhD;
  6. Jos W.R. Meijer, MD, PhD;
  7. Chris J.J. Mulder, MD, PhD;
  8. Coen D.A. Stehouwer, MD, PhD; and
  9. Amado S. Peña, MD, PhD
  1. From Het Groene Hart Ziekenhuis, Gouda; VU University Medical Center, Amsterdam; Rijnstate Hospital, Arnhem; and University Hospital Maastricht, Maastricht, the Netherlands.

    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.

    Article and Author Information

    • Acknowledgment: The authors thank Chad M. Gundy, PhD, Department of Clinical Epidemiology and Biostatistics, VU University Medical Center, for his useful advice and comments.

    • Potential Financial Conflicts of Interest: None disclosed.

    • Requests for Single Reprints: Muhammed Hadithi, MD, Department of Gastroenterology, Het Groene Hart Ziekenhuis, PO Box 1098, 2800 BB Gouda, the Netherlands; e-mail, muhammed.hadithi{at}ghz.nl.

    • Current Author Addresses: Dr. Hadithi: Department of Gastroenterology, Het Groene Hart Ziekenhuis, PO Box 1098, 2800 BB Gouda, the Netherlands.

    • Dr. von Blomberg: Medical Immunology, Department of Pathology, VU University Medical Center, 1007 MB Amsterdam, the Netherlands.

    • Drs. Crusius and Peña: Laboratory of Immunogenetics, Department of Pathology, VU University Medical Center, 1007 MB Amsterdam, the Netherlands.

    • Dr. Bloemena: Department of Pathology, VU University Medical Center, 1007 MB Amsterdam, the Netherlands.

    • Dr. Kostense: Department of Clinical Epidemiology and Biostatistics, VU University Medical Center, 1007 MB Amsterdam, the Netherlands.

    • Dr. Meijer: Department of Pathology, Rijnstate Hospital, PO Box 9555, 6800 TA Arnhem, the Netherlands.

    • Dr. Mulder: Department of Gastroenterology, VU University Medical Center, PO Box 7057, 1007 MB Amsterdam, the Netherlands.

    • Dr. Stehouwer: Department of Internal Medicine, University Hospital Maastricht, PO Box 5800, 6202 AZ Maastricht, the Netherlands.

    • Author Contributions: Conception and design: M. Hadithi, C.D.A. Stehouwer, A.S. Peña.

    • Analysis and interpretation of the data: M. Hadithi, P.J. Kostense, J.W.R. Meijer.

    • Drafting of the article: M. Hadithi, C.D.A. Stehouwer.

    • Critical revision of the article for important intellectual content: M. Hadithi, B.M.E. von Blomberg, J.B.A. Crusius, C.D.A. Stehouwer, A.S. Peña.

    • Final approval of the article: M. Hadithi, C.D.A. Stehouwer, A.S. Peña.

    • Provision of study materials or patients: M. Hadithi, B.M.E. von Blomberg, J.B.A. Crusius, E. Bloemena, J.W.R. Meijer, C.J.J. Mulder, C.D.A. Stehouwer.

    • Statistical expertise: P.J. Kostense.

    • Administrative, technical, or logistic support: M. Hadithi.

    • Collection and assembly of data: M. Hadithi.

    Responses to this article

    • Re: The Confusing Clinical Diagnosis of Celiac Disease
      • Amado Salvador Peña
      Ann Intern Med published online October 26, 2009
    • The Confusing Clinical Diagnosis of Celiac Disease
      • Daniel G. Arkfeld
      Ann Intern Med published online October 26, 2009

    Summary for Patients

    • Summaries for Patients:Accuracy of Serologic Tests and HLA-DQ Typing for Diagnosing Celiac Disease Ann Intern Med September 4, 2007 147:I-34; doi:10.1059/0003-4819-147-5-200709040-00001
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