Indirect and reverse radioimmunoassays and their apparent specificities in the detection of antibodies to enteroviruses in human sera

Abstract

Indirect radioimmunoassays (RIAs) of IgM and IgG antibodies to enteroviruses have been developed, using coxsackieviruses B1 and B3, and echoviruses 11 and 30. The titres of IgM and IgG were assayed in paired sera from patients infected with one of these viruses or coxsackieviruses A7, A9, A16, B2, B4, B5 or echoviruses 4, 17, or 25. Both IgM and IgG were found in almost all serum pairs with each of the four viruses used as an antigen, and there were no certain differences between titres obtained with homologous and heterologous antigens. The convalescent phase specimens contained significantly higher titres compared with the acute phase specimens, the difference being most pronounced for IgG. Of the specimens from patients with nonenterovirus infections, a relatively high percentage contained IgM and IgG against enterovirus antigen. However, no increases in titres were seen between acute and convalescent specimens. When specimens from younger patients, aged 2 days to 22 months, without evidence of enterovirus infections, were assayed with enterovirus antigen, the frequency of IgM titres was seen to increase with age. Almost all specimens from newborns were negative, whereas the specimens from 12- to 22-month-old children showed a high frequency of IgM titres. In specimens from patients aged 2 days to 8 months, the ratio between IgM and IgG titres increased with age, probably due to a loss of maternal IgG. The IgG titres in specimens from 8.5- to 22-month-old children were similar to the titres of specimens from the patients with nonenterovirus infections. A reverse IgM assay was also developed, using the same viruses and serum specimens as for the indirect assays. In contrast to the indirect IgM assay, the reverse IgM assay was apparently type specific, provided that the amount of labeled virus was carefully standardized. The reverse IgM RIA detected and identified antibody responses better than the neutralization test. Attempts to develop a reverse IgG assay were promising concerning the specificity, but the sensitivity was low.

Cross-reactions of immunoglobulin M and G antibodies with enterovirus-specific viral structural proteins

“…Type-specific IgM reactions were found by Schmidt, Magoffin & Lennette (1973) in their gel-diffusion technique in 800 of all positive cases. Schilt (1977) showed for a few sera that IgM antibody-containing serum fractions gave type-specific results in neutralization tests and Torfason, Frisk & Diderholm (1984) reported type-specific reactions in a reverse IgM RIA. The degree of cross-reactivity may be explained by the particular presentation of the antigens in the different systems and, therefore, the results may not be directly comparable.…”

“…Apparently typespecific reactions in a 'reverse IgM RIA' were described by Torfason, Frisk & Diderholm (1984) using purified virions as antigen.…”

Coxsackie B virus-specific IgM antibody and myocardial infarction

“…On the other hand, Katze and Crowell (1980) have shown that the type-specificity of purified coxsackie B viruses is preserved when they attach to a solid phase previously coated with specific 'capture' antibody. That the IgM-antibody-capture technique can be made type-specific was confirmed by Torfason et al (1984) with radiolabelled purified enteroviruses as antigens. However, the antigen dose was critical to avoid cross-reactions.…”

The Swedish childhood diabetes study III: IgM against coxsackie B viruses in newly diagnosed Type 1 (insulin-dependent) diabetic children ? no evidence of increased antibody frequency

“…In the present study an apparently type-specific CBIgM radioimmunoassay [14] has been used. The selection of referent subjects from the population registry matching the index cases which represent consecutive cases in a whole country, makes this study unique.…”