Qualitative Variation among Commercial Immunoassays for Detection of Measles-Specific IgG

Abstract

Measurement of measles virus-specific IgG is used to assess presumptive evidence of immunity among immunocompetent individuals with uncertain immune or vaccination status. False-negative test results may lead to unnecessary quarantine and exclusion from activities such as employment, education, and travel or result in unnecessary revaccination. In contrast, false-positive results may fail to identify susceptible individuals and promote spread of disease by those who are exposed and unprotected. To better understand the performance characteristics of tests to detect measles IgG, we compared five widely used, commercially available measles IgG test platforms using a set of 223 well-characterized serum samples. Measles virus neutralizing antibodies were also measured by in vitro plaque reduction neutralization, the gold standard method, and compared to IgG test results. Discrepant results were observed for samples in the low-positive ranges of the most sensitive tests, but there was good agreement across platforms for IgG-negative sera and for samples with intermediate to high levels of IgG. False-negative test results occurred in approximately 11% of sera, which had low levels of neutralizing antibody.

Keywords: ELISA; IgG; immunity testing; measles; neutralizing antibody; plaque reduction neutralization.

FIG 1

Comparison of quantitative IgG test results with PRN. Measles IgM-negative samples are shown in panels A, C, E, G, and I; measles IgM-positive samples are shown in panels B, D, F, H, and J. The Zeus test had the greatest overall agreement with PRN and was therefore used as a comparator. The platforms tested include Zeus (A and B), Trinity (C and D), Bio-Rad (E and F), bioMérieux Vidas (G and H), and Diasorin (I and J). Horizontal dotted lines indicate cutoffs provided by the test manufacturers. For Diasorin (I and J), the black horizontal lines indicate the cutoff previously used in the United States, and the blue horizontal lines indicate the new cutoff used in the United States and also used in Europe. Vertical dotted lines indicate PRN = 40 and 120 mIU/ml. Samples indicated in red in panels A and B were discrepant between Zeus and at least one other platform. Samples indicated in red in panels C to J were discrepant with the Zeus result.