Recognition, assessment, and management of coeliac disease: summary of updated NICE guidance

In response to Maher et al. the Guideline Development Group (GDG) were aware of the debate between clinical immunologists in the field about appropriate testing standards and received feedback regarding this at consultation; this is elaborated upon in the evidence to recommendation section of the full guideline.
The GDG discussed this issue and their advice was that all of the IgA anti-tTG assays currently in use were developed and validated as assays to detect serum levels of IgA against tTG, where tTG is the antigen. None of these IgA anti-tTG assays were developed and validated to detect total serum levels of IgA, where IgA is the antigen. The use of IgA anti-tTG assays to triage samples for total IgA testing based on the detectable IgA anti-TTG antibody level is the incorrect use of the IgA anti-tTG assays. Using IgA anti-tTG assays to detect a different antigen (IgA) could increase the false-positive rate of the IgA anti-tTG assay. Using the IgA anti-TTG assay in this way relies on the background of the assay and the assumption is that all the background is due to IgA; however this is not the case – the background may be due to rheumatoid factor or due to slightly haemolysed samples.

The paper cited is a case report of a 'serendipitous' detection of a rare immunodeficiency, which does not support the case that 'individuals with detectable IgA anti-TTG antibodies are unlikely to be IgA deficient' and the case discussed did not have detectable IgA anti-TTG antibodies. The case supports reasonable substantiation of the GDG's suggestion that the routine quantitation of serum IgA may have collateral benefits in the identification of immunodeficiencies.

In relation to interpretation of the ISO15189 standards and their application in practice, the GDG's view was that, where a commonly available test has been designed and validated for a particular purpose, it will very seldom be appropriate to rely on an alternative test to derive the same results. It may be that individual laboratories are able to demonstrate adequately validated alternatives to tests that are designed for a particular purpose in line with the standards.

The cost of total IgA testing was not included in modelling the cost-effectiveness of serological strategies, apart from the test’s low absolute cost, as all strategies considered contained an IgA component. In the analysis of which serological test to use in people with symptoms suggestive of coeliac disease, adding a cost (of total IgA) to each strategy would have no influence on the relative cost-effectiveness of the various approaches. However in the analysis of whether to test (in the context of active case finding) an underestimation of the IgA test cost may slightly exaggerate the cost-effectiveness of serological testing in the groups considered.

We agree that the potential for valuable incidental findings are a collateral benefit of measuring IgA levels, and no substitute for appropriate diagnostic process in people suspected of immunodeficiency. However, the GDG noted that, in their experience, suspicion can be raised in this way, and this is an indirect benefit of the approach that should not be completely discounted.

We review our guidelines for update regularly and have passed your comments have been passed to the surveillance review team for consideration at the next review.