Science Bite (3 minute oral presentation with PPT in live session with pre-recorded e-poster) - Students and ECR's only Lorne Infection and Immunity 2022

Dimeric IgA as a novel biomarker of acute measles infection (#60)

Khayriyyah Mohd Hanafiah 1 2 , Heidi Drummer 1 , David Anderson 1
  1. Macfarlane Burnet Institute, Melbourne, Vic, Australia
  2. School of Biological Sciences, Universiti Sains Malaysia, Minden, Penang, Malaysia

Despite tremendous progress in reducing measles incidence through universal vaccine coverage, elimination efforts rely on improved surveillance. Detection of measles-specific immunoglobulin M (IgM) by ELISA is the standard laboratory diagnosis, however, true infection is rare, with most positives being false positives and IgM “true” positivity may also arise following MMR vaccination. This results in low positive predictive values of assays in elimination settings and necessitates confirmatory testing. Improved tests are a WHO research priority. We aimed to determine 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 commercial panel of IgM positives (confirmed acute infected, n=9), a WHO measles IgM proficiency test panel comprising measles IgM positives (which may be either vaccinees or acute infected, n=6), parvo/rubella/dengue IgM positives (n=7), rubella/measles IgM negatives (n=6), provisional diagnosis confirmed measles IgM negatives (n=12) and a panel of blood donors (n=88) on Euroimmun anti-measles virus lysate (VL) and nucleoprotein (NP) IgM kits, then modified for dIgA using an in-house protocol based on a recombinant chimeric secretory component protein and anti-secretory component monoclonal antibody. We report for the first time high levels of anti-measles VL dIgA in the acutely infected group (median S/Co: dIgA: 2.61, IgM: 1.48) and low correlation with IgM levels (R2: 0.019, p value:0.723), although the dIgA ELISA requires further optimisation to reduce false positives (4/88 blood donors). Interestingly, the IgM positives in the WHO proficiency panel had very low levels of anti-measles VL dIgA compared to IgM (median S/Co: dIgA: 0.74, IgM: 1.66) which may represent relative absence of dIgA after vaccination compared to infection, or collection of samples later after acute infection. Among acutely infected individuals of whom 8/9 were anti-measles NP IgM positive, only 1/9 had detectable anti-measles NP dIgA. In one acutely infected donor with multiple time points, anti-measles VL dIgA declined over time while anti-measles VL IgM remained constant. These data suggest that dIgA is an early and transient response in acute measles that warrants further investigation.

  1. Gastañaduy,Paul A; Goodson,James L; Panagiotakopoulos,Lakshmi; Rota,Paul A; Orenstein,Walt A; Patel,Manisha (2021). Measles in the 21st Century: Progress Toward Achieving and Sustaining Elimination. J Infect Dis, 224(Supplement_4) S420-S428.
  2. Brown,David W; Warrener,Lenesha; Scobie,Heather M; Donadel,Morgane; Waku-Kouomou,Diane; Mulders,Mick N; Rota,Paul A (2020). Rapid diagnostic tests to address challenges for global measles surveillance. Curr Opin Virol, 41 77-84.
  3. Rota,Paul A; Moss,William J; Takeda,Makoto; de Swart,Rik L; Thompson,Kimberly M; Goodson,James L (2016). Measles. Nat Rev Dis Primers, 2 16049.
  4. Warrener,Lenesha; Bwogi,Josephine; Andrews,Nick; Samuel,Dhanraj; Kabaliisa,Theopista; Bukenya,Henry; Brown,Kevin; Roper,Martha H; Featherstone,David A; Brown,David (2018). Serum anti-tetanus and measles antibody titres in Ugandan children aged 4 months to 6 years: implications for vaccine programme. Epidemiol Infect, 146(9) 1151-1156.
  5. Hiebert,Joanne; Zubach,Vanessa; Charlton,Carmen L; Fenton,Jayne; Tipples,Graham A; Fonseca,Kevin; Severini,Alberto (2021). Evaluation of Diagnostic Accuracy of Eight Commercial Assays for the Detection of Measles Virus-Specific IgM Antibodies. J Clin Microbiol, 59(6)
  6. Mohd Hanafiah,Khayriyyah; Garcia,Mary L; Barnes,Nadine C; Anderson,David A (2018). Detection of virus-specific polymeric immunoglobulin A in acute hepatitis A, C, E virus serum samples using novel chimeric secretory component. BMC Res Notes, 11(1) 688.
  7. Russell,Michael W; Moldoveanu,Zina; Ogra,Pearay L; Mestecky,Jiri (). Mucosal Immunity in COVID-19: A Neglected but Critical Aspect of SARS-CoV-2 Infection. Front Immunol, 11 611337.