Assessment of variability in IgG subclass ranges in Australian laboratories using survey methodology and battacharya statistics

Abstract

Quantitation of immunoglobulin G (IgG) subclasses has been used in the investigation of immunodeficiency, and more recently, in inflammatory syndromes. Although attempts have been made to standardise reference preparations, marked variability in the ranges quoted in literature and by individual laboratories using the same methodology still occur. We assessed the variation in methodology, reference ranges and reporting in Australian diagnostic laboratories. First we surveyed 25 laboratories subscribing to the RPCA IgG subclass QAP about their methods to determine differences in kit manufacturer, instrument/platform, age related reference ranges, and the source of reference intervals. Second, using a Battacharya statistical method, which identifies overlapping Gaussian distributions on the mathematical separation of healthy and diseased populations, we determined the most appropriate reference ranges for an Australian population. Twenty of 25 (80%) laboratories responded to the survey. Of these, 18 (90%) used a nephelometric method, one (5%) a turbidimetric method and one (5%) radial immunodiffusion (RID). Despite the homogeneity in methodology, reference intervals showed vast inconsistencies, despite the same source being cited by many laboratories. The Bhattacharya method shows wider overall reference intervals for all subclasses when compared with The Binding Site manufacturer’s range, which may affect the utility of this test.