Association between serum levels of total IgA and IgA class endomysial and antigliadin antibodies: Implications for coeliac disease screening

Background: Patients with selective immunoglobulin A (IgA) deficiency and coeliac disease, an established association, lack serum IgA class antigliadin and endomysial antibodies (AGA, EmA). Diagnostic protocols relying on AGA and EmA to select patients for small bower biopsies will not identify these patients. Objective: To determine whether total IgA should be routinely measured in patients suspected of having coeliac disease as a supplementary screening test before biopsy. Design: Prospective measurement of IgA, ACA and EmA in patients undergoing small bowel biopsy for suspected coeliac disease. Patients: We studied 318 patients suspected of having coeliac disease. Sera from 1959 controls in a random population sample were assayed as controls. Results: Thirty-one (10%) patients had villous atrophy, of whom 27 (87%) had EmA. Five (2%) of the 318 patients had undetectable total IgA (< 0.07 g/l): two (40%) of these five had villous atrophy in the setting of negative EmA. Use of undetectable IgA as a selection criterion for small bowel biopsy as well as positive EmA would have improved sensitivity from 87% (27/31) for EmA alone to 94% (29/31), with a fall in positive predictive value from 100% (27/27) to 91% (29/32), but would have maintained high specificity and negative predictive value. Serum IgA was undetectable in 5 (4%) of 117 patients with AGA in the range 0-10 ELISA units (EU) compared with none of 201 with higher AGA (P=0.007, Fisher's exact test). Compared with controls who had AGA 0-10 EU, patients were more likely to have undetectable IgA (5/117 (4%) vs. 3/706 (0.4%): P=0.005). Overall, the median IgA in patients with ACA 0-10 EU was lower than for those with ACA > 10 EU (1.89 g/l vs. 2.34 g/l, P<0.001). Conclusion: There is an association between IgA deficiency and low/negative EmA/ACA. Routine measurement of total serum IgA in patients suspected of having coeliac disease, either with EmA or where ACA is low, improves selection of patients for small bowel biopsy.