Allergy, Asthma and Immunology: Significant, quantifiable differences exist between IgG subclass standards WHO67/97 and ERM-DA470k and can result in different interpretation of results

Clinical Biochemistry

Available online 25 July 2013

In Press, Corrected Proof — Note to users

^a Binding Site Group Limited, 8 Calthorpe Road, Birmingham B15 1QT, United Kingdom
^b Clinical Immunology & Allergy, GSTS Pathology, King's College Hospital, Denmark Hill, London SE5 9RS, United Kingdom
^c Haifa and Western Galilee Laboratory, Clalit Health Services, 47 Hataasia St, Nesher 20300, PO Box 428, Haifa, Israel
^d Département de Biologie Clinique, Cliniques Universitaires Saint Luc, Avenue Hippocrate, 10, 1200 Brussels, Belgium

Open Access

Highlights

•: Samples from four testing sites were measured using commercial IgG subclass assays.
•: The assays are calibrated to two different reference materials.
•: Calibrations were similar for IgG1 and IgG2.
•: For IgG3 and IgG4, the calibrations were significantly different.
•: The two manufacturers' assays can give differing clinical classifications.

Abstract

Objectives

Accurate measurement of IgG subclass (IgGSc) levels are essential to aid in the diagnosis of disease states such as primary immunodeficiencies. However, there is no single standardisation of nephelometric and turbidimetric assays for these analytes and two reference materials have been utilised. We expand on previous reports and present data from a multi-site analysis that both identifies and quantitatively defines the differences in calibration resulting from the use of different reference materials.

Design and methods

IgGSc antibodies in the serum specimens and reference materials were measured according to the manufacturers' instructions using commercially available IgGSc assays or components.

Results

Data from four independent sites showed that in spite of the different commercial suppliers of IgGSc assays calibrating to different reference materials, ERM-DA470k and WHO67 /97, the resulting calibrations were comparable for IgG1 and IgG2. However, for IgG3 and IgG4 the calibrations were significantly different. The use of assay specific normal ranges should compensate for these calibration differences, however, the two manufacturers' assays can give differing clinical classifications. The agreement between the different manufacturers' IgGSc assays was between 85.1% and 95.8% for all IgGSc assays, the discordance of sample classification for IgG1 and IgG2 assays was approximately 12% and 15% respectively, whilst that for IgG3 and IgG4 was 4% and 13% respectively.