Celiac Disease and IGA Deficiency: Complications of Serological Testing Approaches Encountered in the Clinic (Evidence-Based Laboratory Medicine and Test Utilization) (Clinical Report‪)‬

Selective IgA deficiency occurs in 1 of 39 to 57 patients with celiac disease (1-3). This is much higher than the prevalence of selective IgA deficiency in the general population, which is estimated to be approximately 1 in 400 to 18 500, depending on ethnic background (4, 5). Little is known about the prevalence of IgA deficiency in a North American population that undergoes testing for celiac disease by a case-finding strategy. The prevalence of celiac disease in patients with selective IgA deficiency ranges from 10% to 30%, depending on the evaluated population (6-10). This association between celiac disease and IgA deficiency complicates serological testing for celiac disease. Most laboratories offer IgA-based assays only to accomplish serological testing for celiac disease and monitor response (6). If IgA deficiency is not excluded, the physician may not recognize a false-negative celiac serological test result attributable to IgA deficiency (3). Thus, patients with IgA deficiency and celiac disease will remain undetected by the conventional IgA-based serological tests unless IgA concentrations are simultaneously assessed (11, 12). Recommendations regarding the importance of measuring serum IgA concentrations when using an IgA-based test are inconsistent and not always ad dressed in working group proceedings or practice guidelines (13-18 ). Some authors advise excluding IgA deficiency in all patients undergoing serological testing for celiac disease to improve the reliability of a negative test result (1, 3, 18, 19). Others propose that assessment of serum IgA concentrations should be performed only in symptomatic patients because IgA deficiency plus celiac disease occurs in only 1 of 8500 individuals in the general population (14-17). In contrast, some studies conclude that excluding IgA deficiency in all patients adds little value in the detection of celiac disease (20, 21). Confusion about whether celiac disease serological testing should include measurement of serum IgA concentrations is due, at least in part, to the assumption that the issue is the risk of IgA deficiency in the general population rather than the risk in a population that is undergoing testing for celiac disease by a case-finding strategy. To our knowledge, examination of physician practice patterns regarding evaluation and management of IgA deficiency while testing for celiac disease has not been reported. Thus, we evaluated the frequency with which physicians assessed IgA concentrations while performing IgA-based celiac disease serology and the management of negative serology results in IgA-deficient patients. We also examined the prevalence of selective IgA deficiency in a population undergoing celiac disease serological testing by a case-finding strategy and the effect of partial IgA deficiency on the accuracy of IgA-endomysial antibody (EMA)(4) tests.