Antibodies against deamidated gliadin as new and accurate biomarkers of childhood coeliac disease.
OBJECTIVE
Assays of tissue transglutaminase antibodies (anti-tTG) represent the cornerstone of serological coeliac disease (CD) diagnostics. Assays of antibodies against native gliadin (anti-nGli) lost importance due to low validity. We investigated the performance of new assays for antibodies against deamidated gliadin (anti-dGli) in childhood CD.


METHODS
We retrospectively compared children (142 with active CD and 160 without CD, diagnosis confirmed or excluded by intestinal biopsy) concerning (immunoglobulin [Ig] G and IgA) anti-nGli, anti-tTG, and 2 different anti-dGli assays.


RESULTS
IgG-anti-dGli1, IgG-anti-dGli2, and IgA-anti-tTG performed similarly. Area under the receiver-operating characteristic curve (AUC) was 98.6%, 98.9%, and 97.9%; accuracy was 94.7%, 95.7%, and 96.7%. Anti-dGli1 and anti-dGli2 (IgG and IgA) and IgA-anti-tTG performed significantly better than IgA-anti-nGli and IgG-anti-nGli. Both IgG-anti-dGli showed higher AUC and accuracy than IgA-anti-dGli and IgG-anti-tTG. Combined evaluation of IgA-anti-tTG with one of the IgG-anti-dGli tests reduced the rate of falsely classified patients. At enhanced cutoff (specificity >99%), sensitivity was above 67% for both IgG-anti-dGli and IgA-anti-tTG. If IgA-anti-tTG assay was combined with one of the IgG-anti-dGli tests, then the fraction of patients identified with more than 99% specificity as coeliacs increased significantly above 84.5%. Combined evaluation of the 2 IgG-anti-dGli tests did not improve the performance.


CONCLUSIONS
The new IgA and IgG-anti-dGli tests outperform conventional anti-nGli assays. The validity of IgG-anti-dGli cannot be distinguished from IgA-anti-tTG. It should be studied prospectively whether antibody assays could replace biopsy in diagnosis of CD in a substantial segment of children.
Prause
Christian
C
Institute of Laboratory Medicine, Clinical Chemistry, and Molecular Diagnostics, University Hospital, Leipzig, Germany.
Ritter
Maria
M
Probst
Christian
C
Daehnrich
Cornelia
C
Schlumberger
Wolfgang
W
Komorowski
Lars
L
Lieske
Ruediger
R
Richter
Thomas
T
Hauer
Almuthe C
AC
Stern
Martin
M
Uhlig
Holm H
HH
Laass
Martin W
MW
Zimmer
Klaus-Peter
KP
Mothes
Thomas
T
D000577:Amides; D019540:Area Under Curve; D001323:Autoantibodies / Q000097:blood*; D015415:Biomarkers / Q000097:blood; D016022:Case-Control Studies; D002446:Celiac Disease / Q000175:diagnosis* / Q000276:immunology; D002648:Child; D005260:Female; D005903:Gliadin / Q000276:immunology*; D006801:Humans; D008297:Male; D012016:Reference Values; D015203:Reproducibility of Results; D012189:Retrospective Studies; D012680:Sensitivity and Specificity
D000577:Amides; D001323:Autoantibodies; D015415:Biomarkers; D005903:Gliadin