Abstract
Background: The measurement of serum IgE aids in the diagnosis and management of atopic allergic disease and hyper-IgE immunodeficiency syndromes. The 2nd World Health Organization (WHO) International Reference Reagent (IRR) for serum IgE (75/502; 5000 IU/ampoule), is widely used to calibrate assays for serum IgE. Exhaustion of stocks of the 2nd IRR necessitated the production of a replacement preparation and its evaluation in an international collaborative study to determine its suitability to serve as the 3rd International Standard (IS) for serum IgE.
Methods: Sera and defibrinated plasma with elevated IgE levels were pooled and lyophilised in ampoules. This preparation, coded 11/234, was assayed by 18 laboratories in 11 countries using commercial assay methodology for IgE, along with the 2nd IRR, 75/502, and two lyophilised serum samples.
Results: Overall, there were no consistent differences in the way that the candidate IS (11/234), the IRR (75/502), and the two serum samples behaved in the assays with respect to linearity and parallelism. The mean IgE value of the candidate IS, 11/234, relative to the IRR, 75/502, was 13,411 IU/mL based on parallel line analysis of raw assay data at NIBSC, and 13,551 IU/mL based on the laboratories’ own estimates after correcting for the values obtained for 75/502.
Conclusions: The use of 11/234 will ensure that assays for serum IgE continue to be well standardised. The preparation was established by the WHO Expert Committee on Biological Standardization as the 3rd IS for serum IgE with an assigned value of 13,500 IU/mL, corresponding to 6750 IU/ampoule.
Acknowledgments
We thank the staff of the Centre for Biological Reference Materials, NIBSC, for lyophilising the serum IgE bulk and sample despatch.
We are extremely grateful to Dr. Svante Bohman, Phadia, Thermo Fisher Scientific, Sweden, for providing plasma, patients at the Northern General Hospital for donating blood, and the study participants for contributing data.
Conflict of interest statement
Authors’ conflict of interest disclosure: The authors stated that there are no conflicts of interest regarding the publication of this article. Research funding played no role in the study design; in the collection, analysis, and interpretation of data; in the writing of the report; or in the decision to submit the report for publication.
Research funding: None declared.
Employment or leadership: None declared.
Honorarium: None declared.
Appendix
Participants of the collaborative study (in alphabetical order of country).
| Fu Boqiang, National Institute of Metrology, China |
| George Mitis, Nicosia General Hospital, Cyprus |
| Cindy Søndersø Knudsen, Aarhus Universitetshospital, Denmark |
| Christelle Richard, Genclis, France |
| Alf Weimann, Euroimmun AG, Germany |
| Rüdiger Wahl, Omega Diagnostics GmbH, Germany |
| Peter Muench, Roche Diagnostics GmbH, Germany |
| Harald Althaus, Siemens Healthcare Diagnostics, Germany |
| Kafasi Nikolitsa, Laiko General Hospital, Greece |
| Zanoni Giovanna, Universitaria Integrata di Verona, Italy |
| Trude Torsnes, Fürst Medisisnsk Laboratorium, Norway |
| Sivagowri Kasinathan, SSHF Kristiansand, Norway |
| Svante Bohman, Phadia AB, Sweden |
| Nils Burman, Sunderby Hospital, Sweden |
| Matthew Bennett, Genesis Diagnostics Ltd., UK |
| Jackie Donovan, Royal Brompton Hospital, UK |
| Annette Adelmann and James Sackrison, Beckman Coulter Inc., USA |
| Mark Van Cleve and Rosalind Wei, Hycor Biomedical Inc., USA |
Methods used by participating laboratories.
| Laboratory number | Method (as reported by the laboratory) |
|---|---|
| 1 | Phadia ImmunoCAP® Total IgE, |
| Phadia ImmunoCAP® Total IgE low range | |
| 2 | Phadia ImmunoCAP® 250 |
| 3 | ELISA |
| 4 | Chemiluminescence method |
| 5 | Nephelometry (Behring) |
| 6 | Beckman Access 2 – total IgE |
| 7A | ELISA – Radim |
| 7B | Nephelometry BN Prospect, Siemens |
| 8 | Phadia ImmunoCAP® 250 |
| 9 | Heterogeneous Immunoassay (Elecsys) |
| 10 | Phadia ImmunoCAP® 1000 |
| 11 | Microtitre plate ELISA |
| 12 | ELISA |
| 13 | Roche Diagnostics, Cobas e601 |
| 14 | not stated |
| 15 | Microtitre plate ELISA |
| 16 | not stated |
| 17 | ELISA |
| 18 | FEIA (fluorescence enzyme immunoassay) |
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