Abstract

<h3>Introduction</h3> Immunoglobulin A (IgA) deficiency has a population prevalence of 1 in 500–700 individuals. IgA deficiency has been associated with coeliac disease (CD) leading to false negative serological testing. For this reason, NICE have recommended that IgA testing is necessary when case-finding for CD. Scott <i>et al</i> previously modelled the cost-effectiveness of additional IgA measurement on the predictive value of CD screening and found it to be ineffective and unnecessary in improving test predictive outcomes using Fagan9s nomogram at 1 in 50 prevalence. The relationship of IgA deficiency with other autoimmune conditions such as Type 1 diabetes (T1DM) has been poorly quantified. The aim of this study was to assess the prevalence and presenting symptoms of IgA deficiency as defined by levels undetectable by current immunoassay platforms in patients with T1DM and CD. <h3>Methods</h3> We recruited patients with T1DM (n=1000), CD (n=234) and controls who were volunteers from primary care (n=1200). All patients were assessed for CD using antigliadin antibodies (IgA and IgG), IgA endomysial antibodies and IgA anti-tissue transglutaminase antibodies and total IgA levels. IgA deficiency was defined as a total IgA level &lt;0.2 g/l. In each cohort the prevalence of IgA deficiency was calculated and compared. The effect of IgA deficiency on the detection rate of CD was estimated by comparing with duodenal biopsy results. <h3>Results</h3> The prevalence of IgA deficiency in each group was 10/1000 (1%) in those with T1DM, 2/1200 in population control (0.17%) and 4/234 (1.71%) in those with CD. Lack of detectable IgA was more common in both the T1DM group (p=0.015) and the CD group (p=0.008) compared to controls. There was no significant difference in prevalence of IgA deficiency between CD and T1DM (p=0.32). In the T1DM group 33/1000 had CD of which only 1 had IgA deficiency leading to an antibody negative presentation. In the population controls both IgA deficient individuals had normal duodenal biopsies and no relevant symptoms. In the CD group 3 individuals had positive IgG antigliadin antibodies at presentation and all had relevant symptoms. <h3>Conclusion</h3> IgA deficiency is confirmed to be more common in both Type 1 diabetes and coeliac disease compared to population controls at 1 in 100 and 1 in 50 cases. Despite this very few individuals with IgA deficiency alone appear to have underlying villous atrophy on biopsy and therefore contrary to NICE recommendations this strategy may not be cost effective. Few if any IgA deficient patients are likely to be missed if IgA measurement was not made routinely—as most appeared to be asymptomatic.

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