title: Proficiency survey-based evaluation of clinical total and allergen-specific IgE assay performance.
abstract: BACKGROUND
  The diagnostic algorithm for human allergic disease involves confirmation of sensitization by detection of allergen-specific immunoglobulin E (IgE) antibody in individuals suspected of having allergic disease because of a history of allergic symptoms after known allergen exposure. Previous studies showed wide disparity among clinically reported allergen-specific IgE levels from different serologic assays.
  
  
  OBJECTIVE
  To validate the relative analytic performance (sensitivity, interassay reproducibility, linearity/parallelism, intermethod agreement) of clinically used total and allergen-specific IgE assays by using College of American Pathologists' Diagnostic Allergy "SE" Proficiency Survey data.
  
  
  METHODS
  Data from 2 SE survey cycles were used to assess relative analytic performance of the ImmunoCAP (Phadia), Immulite (Siemens Healthcare-Diagnostics), and HYTEC 288 (HYCOR-Agilent Technologies) total and allergen-specific IgE assays. In each cycle, 2 recalcified plasma pools from atopic donors were diluted twice with IgE-negative serum and evaluated in approximately 200 federally certified clinical laboratories for total IgE and IgE antibody to 5 allergen specificities. Statistical analysis evaluated analytic sensitivity, linearity, reproducibility, and intermethod agreement.
  
  
  RESULTS
  Interlaboratory intramethod, intermethod, and interdilution agreement of all 6 clinically used total serum IgE assays were excellent, with coefficients of variation (CVs) below 15%. Interlaboratory intramethod, and interdilution agreement of 3 clinically used allergen-specific IgE assays were also excellent with CVs below 15%. However, intermethod CVs identified between-assay disagreement greater than 20% in 80% of allergen-specific IgE measurements. Allergen reagents and patients' immune response heterogeneity are suggested probable causes.
  
  
  CONCLUSIONS
  Clinical total and allergen-specific IgE assays display excellent analytic sensitivity, precision, reproducibility, and linearity. Marked variability in quantitative estimates of allergen-specific IgE from clinically used automated immunoassays is a concern that may be ameliorated with component allergen use.
authors.affiliation: Departments of Pathology and Medicine, Johns Hopkins University School of Medicine, Johns Hopkins Asthma and Allergy Center, 5501 Hopkins Bayview Circle, Baltimore, MD 21224, USA. rhamilt2@jhmi.edu
authors.forename: Robert G
authors.initials: RG
authors.lastname: Hamilton
mesh_terms: D000485:Allergens / Q000276:immunology*; D000939:Epitopes; D006801:Humans; D006967:Hypersensitivity / Q000097:blood / Q000175:diagnosis*; D007073:Immunoglobulin E / Q000097:blood* / Q000276:immunology*; D010336:Pathology / Q000379:methods* / Q000592:standards; D015203:Reproducibility of Results; D012680:Sensitivity and Specificity; D012955:Societies, Medical; D014481:United States
chemical_list: D000485:Allergens; D000939:Epitopes; D007073:Immunoglobulin E