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Transglutaminase Iga Antibodies in A Celiac Disease Mass Screening and the Role of Hla-Dq Genotyping and Endomysial Antibodies in Sequential Testing.

Sandström, Olof ; Rosenquist, Anna LU ; Lagerqvist, Carina ; Carlsson, Annelie LU ; Hernell, Olle ; Högberg, Lotta and Ivarsson, Anneli (2013) In Journal of Pediatric Gastroenterology and Nutrition - Jpgn 57(4). p.472-476
Abstract
OBJECTIVES:: To evaluate hypothetical screening strategies in a Swedish celiac disease (CD) mass screening. PATIENTS AND METHODS:: Out of 10041 Swedish sixth-graders born in 1993 invited to a population-based CD mass screening, 7208 participated. Anti-tissue-transglutaminase (tTG) IgA were analyzed in all children and total serum IgA (s-IgA) in 7161 children. Additional analyses of tTG-IgG, endomysial antibodies (EMA) IgA and IgG, and human leukocyte antigen (HLA) alleles were performed according to a standardized protocol. Children with elevated levels of serological markers were recommended to undergo a small intestinal biopsy to verify diagnosis and 153 children with CD were thus identified. Sensitivity, specificity, positive (PPV) and... (More)
OBJECTIVES:: To evaluate hypothetical screening strategies in a Swedish celiac disease (CD) mass screening. PATIENTS AND METHODS:: Out of 10041 Swedish sixth-graders born in 1993 invited to a population-based CD mass screening, 7208 participated. Anti-tissue-transglutaminase (tTG) IgA were analyzed in all children and total serum IgA (s-IgA) in 7161 children. Additional analyses of tTG-IgG, endomysial antibodies (EMA) IgA and IgG, and human leukocyte antigen (HLA) alleles were performed according to a standardized protocol. Children with elevated levels of serological markers were recommended to undergo a small intestinal biopsy to verify diagnosis and 153 children with CD were thus identified. Sensitivity, specificity, positive (PPV) and negative predictive values (NPV) were calculated and receiver operating characteristic (ROC) curves were plotted. RESULTS:: By lowering the cutoff for tTG-IgA, 17 additional cases of CD were identified at the cost of 32 biopsies. All children with tTG-IgA above 50U/mL (10 times the recommended upper limit of normal) had gluten enteropathy. Area under the ROC curve for tTG-IgA was 0.988. All cases carried HLA-DQ2 or HLA-DQ8, as did 53% of the controls. For different hypothetical screening strategies sensitivity, specificity, PPV and NPV ranged between 87.6-100%, 99.5- 99.9%, 79.7-89.7% and 99.7-100%, respectively. Efforts to increase sensitivity by lowering tTGIgA cut-would result in increased number of small intestinal biopsies and lower PPV. Sequential testing for both EMA and HLA-DQ genotyping would reduce the number of negative small intestinal biopsies. CONCLUSIONS:: tTG-IgA is a robust marker when used in CD mass screening and its performance can be enhanced by sequential testing for EMA or HLA-DQ genotyping. (Less)
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organization
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type
Contribution to journal
publication status
published
subject
in
Journal of Pediatric Gastroenterology and Nutrition - Jpgn
volume
57
issue
4
pages
472 - 476
publisher
Lippincott Williams & Wilkins
external identifiers
  • wos:000326745500020
  • pmid:23783015
  • scopus:84885310783
ISSN
1536-4801
DOI
10.1097/MPG.0b013e31829ef65d
language
English
LU publication?
yes
id
5d68e408-0f13-4fc9-97d2-33e85ebd3047 (old id 3913173)
alternative location
http://www.ncbi.nlm.nih.gov/pubmed/23783015?dopt=Abstract
date added to LUP
2016-04-01 11:00:41
date last changed
2020-07-15 01:37:33
@article{5d68e408-0f13-4fc9-97d2-33e85ebd3047,
  abstract     = {OBJECTIVES:: To evaluate hypothetical screening strategies in a Swedish celiac disease (CD) mass screening. PATIENTS AND METHODS:: Out of 10041 Swedish sixth-graders born in 1993 invited to a population-based CD mass screening, 7208 participated. Anti-tissue-transglutaminase (tTG) IgA were analyzed in all children and total serum IgA (s-IgA) in 7161 children. Additional analyses of tTG-IgG, endomysial antibodies (EMA) IgA and IgG, and human leukocyte antigen (HLA) alleles were performed according to a standardized protocol. Children with elevated levels of serological markers were recommended to undergo a small intestinal biopsy to verify diagnosis and 153 children with CD were thus identified. Sensitivity, specificity, positive (PPV) and negative predictive values (NPV) were calculated and receiver operating characteristic (ROC) curves were plotted. RESULTS:: By lowering the cutoff for tTG-IgA, 17 additional cases of CD were identified at the cost of 32 biopsies. All children with tTG-IgA above 50U/mL (10 times the recommended upper limit of normal) had gluten enteropathy. Area under the ROC curve for tTG-IgA was 0.988. All cases carried HLA-DQ2 or HLA-DQ8, as did 53% of the controls. For different hypothetical screening strategies sensitivity, specificity, PPV and NPV ranged between 87.6-100%, 99.5- 99.9%, 79.7-89.7% and 99.7-100%, respectively. Efforts to increase sensitivity by lowering tTGIgA cut-would result in increased number of small intestinal biopsies and lower PPV. Sequential testing for both EMA and HLA-DQ genotyping would reduce the number of negative small intestinal biopsies. CONCLUSIONS:: tTG-IgA is a robust marker when used in CD mass screening and its performance can be enhanced by sequential testing for EMA or HLA-DQ genotyping.},
  author       = {Sandström, Olof and Rosenquist, Anna and Lagerqvist, Carina and Carlsson, Annelie and Hernell, Olle and Högberg, Lotta and Ivarsson, Anneli},
  issn         = {1536-4801},
  language     = {eng},
  number       = {4},
  pages        = {472--476},
  publisher    = {Lippincott Williams & Wilkins},
  series       = {Journal of Pediatric Gastroenterology and Nutrition - Jpgn},
  title        = {Transglutaminase Iga Antibodies in A Celiac Disease Mass Screening and the Role of Hla-Dq Genotyping and Endomysial Antibodies in Sequential Testing.},
  url          = {http://dx.doi.org/10.1097/MPG.0b013e31829ef65d},
  doi          = {10.1097/MPG.0b013e31829ef65d},
  volume       = {57},
  year         = {2013},
}