Discrepancies between histology and serology for the diagnosis of coeliac disease (2)
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* Oscar MP Jolobe

Editor – Discrepancies between histology and serology for the diagnosis of coeliac disease (CD) (Clin Med August 2009 pp 346–8) are inevitable, given the fact that, even measurement of transglutaminase autoantibodies (TGAA), the latter now considered to be the most efficient single test for CD,1,2 generated variable diagnostic accuracy in a workshop designated to compare test performance for TGAA among 20 institutions, comprising five commercial and 15 research and clinical laboratories. In that study six laboratories contributed sera from individuals with CD as defined by accepted clinical criteria including small bowel biopsy, and these were compared with healthy control sera from individuals not known to have CD or type 1 diabetes. Assays for TGAA included enzyme-linked immunosorbent assay (ELISA) and radiobinding assays (RBA). Laboratory sensitivity ranged from 69% to 93%, and specificity ranged from 96% to 100%. The highest sensitivity (93%) with 100% specificity was achieved by two radiobinding assays, and RBA identified sera from CD patients as positive with greater frequency than did ELISA. Nevertheless, ELISA assays together provided less variation in ‘signal-to-noise’ than did RBA. However, for the coeliac samples between different laboratories performing ELISA, linear correlation, r-squared, ranged from 0.4244 to 0.8882.3 What has also emerged is that the age-related differences documented in the clinical and histological stigmata of CD, have, as a corollary, a correlation between TGAA levels and degree of villous atrophy. This was shown in a study where severe villous atrophy (Marsh IIIB and IIIC) was significantly (p,0.0001) more prevalent in children than in adults. In that study, a significant correlation was also established between IgA TGAA titres and age (Pearson coefficient50.524; p,0.001), and also between IgA TGAA titres and degree of villous atrophy (Spearman rho50.59; p,0.001).4 Accordingly, given the fact that concordance between histology and serology depends, not only on the performance and methodology of the laboratory performing the serological tests, but also on patient characteristics, histology should continue to be the ‘gold standard’ for diagnosis of CD.

## Footnotes

*   Please submit letters for the Editor's consideration within three weeks of receipt of the Journal. Letters should ideally be limited to 350 words, and sent by email to: Clinicalmedicine{at}rcplondon.ac.uk

*   © 2010 Royal College of Physicians

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# Discrepancies between histology and serology for the diagnosis of coeliac disease (2) {#article-title-6}

We would like to thank the respondents for their helpful insights and comments which offer several plausible explanations for the discrepancy we observed between serological and histological testing for coeliac disease (CD). The ELISA-based IgA anti-tissue transglutaminase (anti-tTG) assay used at Medway Hospital is typical of that used at many peripheral centres. Although an antibody radiobinding assay for measuring IgA antibodies to human tissue transglutaminase has been shown to achieve a sensitivity and specificity at least equivalent to endomysial antibody,1 it is not readily available. It is therefore common practice to combine serological testing in order to improve sensitivity and specificity.2 The positive and negative predictive value of combining IgA anti-tTG antibodies and IgA anti-endomysial antibodies has been reported to be over 95%.3 A multicentre European study showed that out of 126 biopsy-confirmed cases with CD, eight (6.4%) had negative combined IgA anti-tTG (ELISA-based) and IgA anti-endomysial antibodies.4 We accept that the IgA and IgG anti-gliadin antibody assay is no longer used in most centres due to reduced sensitivity and specificity, and serological testing at Medway hospital has since been changed to IgA and IgG anti-endomysial antbody and IgA and IgG anti-tissue transglutaminase. Furthermore, although none of the patients were known to be on a formal gluten free diet, it is possible that some may have reduced their gluten intake prior to serology testing.

We fully accept that our false negative rate for serology should be interpreted with caution and because of the small numbers, may overestimate the magnitude of the problem. Never the less, it would be surprising if this finding was unique to our hospital. There is often a long delay in diagnosis ranging from 4.9 to 11 years,5,6 as illustrated by our case study and the increasing reliance on non-invasive testing means that patients will remain undiagnosed. What is clear is that we all agree that it is important for physicians to be aware of the more protean presentations of CD, the limitations of serology and the importance of a duodenal biopsy in making the diagnosis of CD.

## Footnotes

*   Please submit letters for the Editor's consideration within three weeks of receipt of the Journal. Letters should ideally be limited to 350 words, and sent by email to: Clinicalmedicine{at}rcplondon.ac.uk

*   © 2010 Royal College of Physicians

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