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

Research output: Contribution to journalArticleAcademicpeer-review

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.

Original languageEnglish
Pages (from-to)294-302
Number of pages9
JournalAnnals of Internal Medicine
Volume147
Issue number5
Publication statusPublished - 4 Sep 2007

Cite this

Hadithi, M., von Blomberg, B. M. E., Crusius, J. B. A., Bloemena, E., Kostense, P. J., Meijer, J. W. R., ... Peña, A. S. (2007). Accuracy of serologic tests and HLA-DQ typing for diagnosing celiac disease. Annals of Internal Medicine, 147(5), 294-302.
Hadithi, Muhammed ; von Blomberg, B Mary E ; Crusius, J Bart A ; Bloemena, Elisabeth ; Kostense, Pieter J ; Meijer, Jos W R ; Mulder, Chris J J ; Stehouwer, Coen D A ; Peña, Amado S. / Accuracy of serologic tests and HLA-DQ typing for diagnosing celiac disease. In: Annals of Internal Medicine. 2007 ; Vol. 147, No. 5. pp. 294-302.
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title = "Accuracy of serologic tests and HLA-DQ typing for diagnosing celiac disease",
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.",
keywords = "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",
author = "Muhammed Hadithi and {von Blomberg}, {B Mary E} and Crusius, {J Bart A} and Elisabeth Bloemena and Kostense, {Pieter J} and Meijer, {Jos W R} and Mulder, {Chris J J} and Stehouwer, {Coen D A} and Pe{\~n}a, {Amado S}",
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Hadithi, M, von Blomberg, BME, Crusius, JBA, Bloemena, E, Kostense, PJ, Meijer, JWR, Mulder, CJJ, Stehouwer, CDA & Peña, AS 2007, 'Accuracy of serologic tests and HLA-DQ typing for diagnosing celiac disease' Annals of Internal Medicine, vol. 147, no. 5, pp. 294-302.

Accuracy of serologic tests and HLA-DQ typing for diagnosing celiac disease. / Hadithi, Muhammed; von Blomberg, B Mary E; Crusius, J Bart A; Bloemena, Elisabeth; Kostense, Pieter J; Meijer, Jos W R; Mulder, Chris J J; Stehouwer, Coen D A; Peña, Amado S.

In: Annals of Internal Medicine, Vol. 147, No. 5, 04.09.2007, p. 294-302.

Research output: Contribution to journalArticleAcademicpeer-review

TY - JOUR

T1 - Accuracy of serologic tests and HLA-DQ typing for diagnosing celiac disease

AU - Hadithi, Muhammed

AU - von Blomberg, B Mary E

AU - Crusius, J Bart A

AU - Bloemena, Elisabeth

AU - Kostense, Pieter J

AU - Meijer, Jos W R

AU - Mulder, Chris J J

AU - Stehouwer, Coen D A

AU - Peña, Amado S

PY - 2007/9/4

Y1 - 2007/9/4

N2 - 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.

AB - 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.

KW - Adult

KW - Autoantibodies/blood

KW - Biopsy

KW - Celiac Disease/diagnosis

KW - Enzyme-Linked Immunosorbent Assay

KW - Female

KW - Fluorescent Antibody Technique, Indirect

KW - Genotype

KW - Gliadin/immunology

KW - Glycoside Hydrolases/immunology

KW - HLA-DQ Antigens/genetics

KW - Humans

KW - Immunologic Tests

KW - Intestine, Small/pathology

KW - Male

KW - Middle Aged

KW - Prospective Studies

KW - Transglutaminases/immunology

M3 - Article

VL - 147

SP - 294

EP - 302

JO - Annals of Internal Medicine

JF - Annals of Internal Medicine

SN - 0003-4819

IS - 5

ER -

Hadithi M, von Blomberg BME, Crusius JBA, Bloemena E, Kostense PJ, Meijer JWR et al. Accuracy of serologic tests and HLA-DQ typing for diagnosing celiac disease. Annals of Internal Medicine. 2007 Sep 4;147(5):294-302.