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Immunoassays for the detection of IgA antibodies to tissue transglutaminase: significance of multiples of the upper limit of normal and inter-assay correlations

  • Brenda B. Suh-Lailam , K. Wayne Davis and Anne E. Tebo EMAIL logo
Published/Copyright: July 14, 2015
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Clinical Chemistry and Laboratory Medicine (CCLM)
From the journal Clinical Chemistry and Laboratory Medicine (CCLM) Volume 54 Issue 2

Abstract

Background: The presence of IgA antibodies to tissue transglutaminase (anti-tTg) is associated with variable risk for celiac disease. The use of common multiples of the upper limit of normal (ULN) has been suggested to optimize diagnostic pathways as well as improve harmonization between assays.

Methods: The characteristics of four anti-tTG IgA assays relative to endomysial IgA (EMA) by indirect immunofluorescence assay (IFA) as reference test were assessed. Commutability between anti-tTG immunoassays and/or EMA based on manufacturer’s recommended cut-off values and three common multiples of ULN (3×, 5× and 10×) was also investigated. Sera from 200 patients and 100 healthy individuals were analyzed.

Results: At manufacturer’s cut-off; the sensitivities for the tTG assays ranged from 72.5% to 98.6% and specificities from 60.3% to 99.2%. The percent positive agreements between any anti-tTG and EMA or any two anti-tTG immunoassays varied from 56.7% to 98.0% and 46.7% to 100.0%, respectively. At 3×, 5× or 10× ULNs, the inter-rater reliability as measured by Cohen κ between any two anti-tTG assays were quite variable and ranged from 0.28 to 0.96, 0.26 to 0.89 or 0.13 to 0.78, respectively. Furthermore, the percent positive agreements between any two anti-tTg IgA immunoassays ranged from 83.1% to 98.2%, 92.0% to 100%, or 100%, at 3×, 5× or 10×, respectively.

Conclusions: Commutability between tTG IgA immunoassays or tTG IgA and EMA is kit-dependent and common multiples of the ULN are not sufficient to correct for inter-assay variations. Many factors influence the performance of anti-tTG IgA assays which limit their commutability.

Keywords: antibodies; immunoassay; tissue transglutaminase; upper limit of normal
Corresponding author: Anne E. Tebo, PhD, ARUP Laboratories, 500 Chipeta Way, Salt Lake City, UT 84108-1221, USA, Phone: +1 801 5832787 ext 3138, E-mail: ; ARUP Institute for Clinical and Experimental Pathology, Salt Lake City, UT, USA; and Department of Pathology, University of Utah School of Medicine, Salt Lake City, UT, USA

Acknowledgments

We would like to thank the staff of the Autoimmune Immunology Section of ARUP Laboratories for the technical assistance and Elisabeth Malmberg, ARUP Institute for Clinical and Experimental Pathology for statistical support. The authors also acknowledge material support from INOVA Diagnostics and Phadia. This work was supported by the ARUP Institute for Clinical and Experimental Pathology, Salt Lake City, Utah.

Author contributions: All the authors have accepted responsibility for the entire content of this submitted manuscript and approved submission.

Research funding: None declared.

Employment or leadership: None declared.

Honorarium: None declared.

Competing interests: The funding organization(s) played no role in the study design; in the collection, analysis, and interpretation of data; in the writing of the report; or in the decision to submit the report for publication.

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Received: 2015-4-13
Accepted: 2015-6-10
Published Online: 2015-7-14
Published in Print: 2016-2-1

©2016 by De Gruyter

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https://doi.org/10.1515/cclm-2015-0348
Keywords for this article
antibodies; immunoassay; tissue transglutaminase; upper limit of normal

Articles in the same Issue

  1. Frontmatter
  2. Editorial
  3. Total error vs. measurement uncertainty: the match continues
  4. Review
  5. Application of fatty acid and lipid measurements in neuropsychiatry
  6. Mini Review
  7. The Janus faces of acquired angioedema: C1-inhibitor deficiency, lymphoproliferation and autoimmunity
  8. Opinion Papers
  9. How to report results of prothrombin and activated partial thromboplastin times
  10. Useful measures and models for analytical quality management in medical laboratories
  11. Total error vs. measurement uncertainty: revolution or evolution?
  12. Genetics and Molecular Diagnostics
  13. Rapid detection of Mmalton α1-antitrypsin deficiency allele by real-time PCR and melting curves in whole blood, serum and dried blood spot samples
  14. General Clinical Chemistry and Laboratory Medicine
  15. Diagnostic and clinical significance of Crohn’s disease-specific pancreatic anti-GP2 and anti-CUZD1 antibodies
  16. Immunoassays for the detection of IgA antibodies to tissue transglutaminase: significance of multiples of the upper limit of normal and inter-assay correlations
  17. Effects of biobanking conditions on six antibiotic substances in human serum assessed by a novel evaluation protocol
  18. Haematology and Coagulation
  19. Measurement of dabigatran, rivaroxaban and apixaban in samples of plasma, serum and urine, under real life conditions. An international study
  20. Reference Values and Biological Variations
  21. Upper reference limits for cerebrospinal fluid total protein and albumin quotient based on a large cohort of control patients: implications for increased clinical specificity
  22. Reference intervals for bone turnover markers in Spanish premenopausal women
  23. Cancer Diagnostics
  24. Citrulline as a biomarker of gastrointestinal toxicity in patients with rectal carcinoma treated with chemoradiation
  25. mRNA overexpression of kallikrein-related peptidase 14 (KLK14) is an independent predictor of poor overall survival in chronic lymphocytic leukemia patients
  26. Cardiovascular Diseases
  27. TBX20 loss-of-function mutation associated with familial dilated cardiomyopathy
  28. Cardiac troponin I release after a basketball match in elite, amateur and junior players
  29. The role of timely measurement of galectin-3, NT-proBNP, cystatin C and hsTnT in predicting prognosis and heart function after heart transplantation
  30. Infectious Diseases
  31. Neutrophil CD64 combined with PCT, CRP and WBC improves the sensitivity for the early diagnosis of neonatal sepsis
  32. A comparison of three commercial platforms for urinary NGAL in critically ill adults
  33. Diabetes
  34. Liquid citrate acidification introduces significant glucose bias and leads to misclassification of patients with diabetes
  35. Letter to the Editors
  36. A rare and unstable hemoglobin variant, Hb M Dothan β 25/26 (-GTG), detected by the anomalous cytogram on Sysmex XE-2100
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