title: Celiac disease and IgA deficiency: complications of serological testing approaches encountered in the clinic.
abstract: BACKGROUND
  IgA deficiency causes false-negative IgA-based celiac serology results in patients with celiac disease. Using a case-finding strategy, we examined the prevalence of IgA deficiency, physician evaluation, and management of IgA deficiency during serological testing for celiac disease.
  
  
  METHODS
  We reviewed consecutive IgA-endomysial antibody (EMA) and serum IgA results from the laboratory database over 17 months. We cross-referenced seronegative patients with IgA deficiency (IgA <0.06 g/L) to the pathology database to evaluate intestinal biopsy results. Ordering physicians received a questionnaire regarding the management of seronegative patients with IgA deficiency who had no biopsy record.
  
  
  RESULTS
  Among the 9533 patients tested for IgA-EMA, 4698 (49%) were tested for IgA deficiency. IgA deficiency occurred in 35 of 4698 (0.75%) patients screened for IgA deficiency. Only 19 of 35 (54%) IgA-deficient patients were diagnosed appropriately with either intestinal biopsy (17 patients) or measurement of IgG-tissue transglutaminase (2 patients). Thirteen (76%) of the 17 IgA-deficient patients who underwent upper endoscopy with or without colonoscopy displayed gastrointestinal pathology on biopsies, including 3 (18%) with celiac disease. No further evaluation to exclude celiac disease was performed for the remaining 16 of 35 (46%) IgA-deficient, EMA-negative patients because of inappropriate management (6 patients), administrative error (7 patients), or patient/physician refusal (3 patients).
  
  
  CONCLUSIONS
  IgA deficiency occurred in 1:131 patients tested for celiac disease, and celiac disease occurred in 1:6 of those properly evaluated. Inadequate evaluation of IgA deficiency while testing for celiac disease occurred frequently and resulted in the underdiagnosis of both. Changes in testing algorithms and reporting of results were made to improve testing for celiac disease and IgA deficiency.
authors.affiliation: Department of Pediatrics, University of Calgary, Calgary, Alberta, Canada.
authors.forename: Kelly E
authors.initials: KE
authors.lastname: McGowan
authors.forename: Martha E
authors.initials: ME
authors.lastname: Lyon
authors.forename: J Decker
authors.initials: JD
authors.lastname: Butzner
mesh_terms: D000293:Adolescent; D000328:Adult; D000368:Aged; D001323:Autoantibodies / Q000097:blood*; D002446:Celiac Disease / Q000150:complications / Q000175:diagnosis*; D002648:Child; D002675:Child, Preschool; D005188:False Negative Reactions; D005260:Female; D006801:Humans; D017098:IgA Deficiency / Q000150:complications / Q000175:diagnosis* / Q000453:epidemiology; D007070:Immunoglobulin A / Q000097:blood* / Q000276:immunology; D008297:Male; D008875:Middle Aged; D000091345:Protein Glutamine gamma Glutamyltransferase 2; D012698:Serologic Tests
chemical_list: D001323:Autoantibodies; D007070:Immunoglobulin A; C000717608:TGM2 protein, human; D000091345:Protein Glutamine gamma Glutamyltransferase 2