Sensitivity and specificity of viral immunoglobulin M determination by indirect enzyme-linked immunosorbent assay.
Four sources of error associated with virus-specific immunoglobulin M (IgM) determination by indirect enzyme-linked immunosorbent assay were recognized and analyzed. First, competitive inhibition due to specific IgG was demonstrated by experiments involving addition and subtraction of rubella-specific IgG. Second, the interference due to rheumatoid factors (RFs) of the IgM class (IgM-RFs) was studied thoroughly, and it appeared that the level of false positivity was more dependent on specific IgG titers than on IgM-RF titers. Third, it was found that some IgM-RFs, differing from conventional IgM-RFs in that they reacted only with isologous IgG, were responsible for further cases of false positivity. Fourth, the interference of an IgM reacting with some virus-unmasked cellular antigens was demonstrated for some uninfected individuals. All four interfering factors could be readily eliminated by simply premixing serum samples with a sheep anti-human gamma-chain serum. This single pretreatment was shown to eliminate false-negatives as well as false-positives in a further 2,004 sera tested for six viruses. These results also emphasize the frequency of RFs and their heterogeneity.
D000914:Antibodies, Viral / Q000032:analysis; D000918:Antibody Specificity; D001667:Binding, Competitive; D004306:Dose-Response Relationship, Immunologic; D004797:Enzyme-Linked Immunosorbent Assay; D005188:False Negative Reactions; D005189:False Positive Reactions; D006801:Humans; D007074:Immunoglobulin G / Q000276:immunology; D007075:Immunoglobulin M / Q000032:analysis*; D011237:Predictive Value of Tests; D012217:Rheumatoid Factor / Q000276:immunology; D012412:Rubella virus / Q000276:immunology*; D014780:Viruses / Q000276:immunology*
D000914:Antibodies, Viral; D007074:Immunoglobulin G; D007075:Immunoglobulin M; C040901:rubella antibodies; D012217:Rheumatoid Factor