title: Investigation into low-level anti-rubella virus IgG results reported by commercial immunoassays.
abstract: Since the 1980s, commercial anti-rubella virus IgG assays have been calibrated against a WHO International Standard and results have been reported in international units per milliliter (IU/ml). Laboratories testing routine patients' samples collected 100 samples that gave anti-rubella virus IgG results of 40 IU/ml or less from each of five different commercial immunoassays (CIA). The total of 500 quantitative results obtained from 100 samples from each CIA were compared with results obtained from an in-house enzyme immunoassay (IH-EIA) calibrated using the WHO standard. All 500 samples were screened using a hemagglutination inhibition assay (HAI). Any sample having an HAI titer of 1:8 or less was assigned a negative anti-rubella virus antibody status. If the HAI titer was greater than 1:8, the sample was tested in an immunoblot (IB) assay. If the IB result was negative, the sample was assigned a negative anti-rubella virus IgG status; otherwise, the sample was assigned a positive status. Concordance between the CIA qualitative results and the assigned negative status ranged from 50.0 to 93.8% and 74.5 to 97.8% for the assigned positive status. Using a receiver operating characteristic analysis with the cutoff set at 10 IU/ml, the estimated sensitivity and specificity ranged from 70.2 to 91.2% and 65.9 to 100%, respectively. There was poor correlation between the quantitative CIA results and those obtained by the IH-EIA, with the coefficient of determination (R(2)) ranging from 0.002 to 0.413. Although CIAs have been calibrated with the same international standard for more than 2 decades, the level of standardization continues to be poor. It may be time for the scientific community to reevaluate the relevance of quantification of anti-rubella virus IgG.
authors.affiliation: NRL, Melbourne Australia, Victoria, Australia. wayne@nrl.gov.au
authors.forename: Wayne
authors.initials: W
authors.lastname: Dimech
authors.forename: Nilukshi
authors.initials: N
authors.lastname: Arachchi
authors.forename: Jingjing
authors.initials: J
authors.lastname: Cai
authors.forename: Terri
authors.initials: T
authors.lastname: Sahin
authors.forename: Kim
authors.initials: K
authors.lastname: Wilson
mesh_terms: D000914:Antibodies, Viral / Q000097:blood* / Q000276:immunology; D006385:Hemagglutination Inhibition Tests; D006801:Humans; D007118:Immunoassay / Q000592:standards; D015151:Immunoblotting; D007074:Immunoglobulin G / Q000032:analysis / Q000097:blood* / Q000276:immunology; D012372:ROC Curve; D012015:Reference Standards; D012016:Reference Values; D012409:Rubella / Q000175:diagnosis*; D012412:Rubella virus / Q000276:immunology*; D012680:Sensitivity and Specificity
chemical_list: D000914:Antibodies, Viral; D007074:Immunoglobulin G; C040901:rubella antibodies