Advances in Plasma Protein Standardization

For several years quality assessment schemes have shown poor inter-laboratory agreement for the measurement of plasma proteins. There are many possible explanations for this phenomenon but these can be classified under three main headings: molecular heterogeneity of plasma proteins, type of assay and heterogeneity of antisera used for quantitation; and the standard(s) used to calibrate the test system.' The problem of variability due to standardization was recognized by Rowe et al. in 1970.2,3 They distributed six coded serum samples to several expert laboratories for measurement of IgG, IgA and IgM. For the same samples laboratories reported results with ratios of the highest to lowest values of 2·2-fold for IgG, 3'2-fold for IgA and 5'0-fold for IgM. When all laboratories used a common arbitrary reference standard the highest to lowest value ratios decreased to 1'36-fold for IgG, 1·17-fold for IgA and 1'31-fold for IgM. The authors proposed that greater uniformity of plasma immunoglobulin results should be achieved if the World Health Organization (WHO) International Reference Preparation for Human Serum Immunoglobulins G, A and M was in general use. Subsequently, a number of international primary and secondary reference preparations was prepared and distributed but the use of these materials did not entirely remove the problem of inter-laboratory differences in plasma protein measurement. By proposed definition, a Certified Reference Material (CRM) is a 'reference material accompanied by, or traceable to, a certificate stating the property value(s) concerned, issued by an organisation, public or private, which is generally accepted as technically competent'. Such materials are often, but not invariably, primary