Dimeric immunoglobulin A as a novel diagnostic marker of measles infection

Abstract

Despite tremendous measles incidence reduction through universal vaccination, elimination efforts rely on improved surveillance. Detection of anti-measles immunoglobulin M (IgM) by ELISA is the standard laboratory diagnostic method. However, true infection is rare and seroconversion following MMR vaccination also generates IgM, which results in low positive predictive values of assays in elimination settings, thus necessitating confirmatory testing. Improved diagnostic tests for measles infection are a World Health Organization (WHO) research priority. We investigated whether dimeric immunoglobulin A (dIgA), the predominant antibody produced in mucosal immunity, may be a marker of recent or acute measles infection. We examined a serological panel of confirmed measles infection (anti-measles IgM positives, n=50), and non-measles infection with rubella (n=36), roseola (n=40), chikungunya/dengue/zika (n=41), parvovirus (n=35) and other fever-rash illness of unknown cause (n=37). Sera were examined on a Micrommune anti-measles IgM, Euroimmun anti-measles virus lysate (VL) and nucleoprotein (NP) IgM kits. Assays were then modified to detect dIgA using an in-house protocol based on a recombinant chimeric secretory component protein and anti-secretory component monoclonal antibody. We observed significantly higher levels of anti-measles VL dIgA in measles samples than non-measles controls (p<0.001), and there was low correlation with IgM (R2: 0.01, p value:0.487). Unlike IgM, dIgA reactive to measles NP was not detected in most samples. Comparable diagnostic potential of anti-measles dIgA (AUC 0.920 - 0.945) to anti-measles IgM (AUC 0.986 – 0.995), suggests that dIgA may be a new blood-based marker of acute measles, independent of IgM, which merits further investigation and optimization.