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

4 September 2007 | Volume 147 Issue 5 | Pages 294-302

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.

Editors' Notes Context The value of adding HLA genetic typing to serologic testing for celiac disease is not well defined. Contribution In this prospective study of patients referred for evaluation of celiac disease, the test performance of combinations of genetic typing and serologic testing was similar to that of either strategy alone. Caution The small number of cases of celiac disease precluded meaningful comparisons of testing strategies. Implications The combination of genetic typing and serologic testing is about as accurate as either strategy alone. Neither is a substitute for small-bowel biopsy in the diagnosis of celiac disease. —The Editors

 

Author and Article Information

From Het Groene Hart Ziekenhuis, Gouda; VU University Medical Center, Amsterdam; Rijnstate Hospital, Arnhem; and University Hospital Maastricht, Maastricht, the Netherlands.

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.

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