An evaluation under code of new techniques for the detection of cytomegalovirus antibodies: sensitivity of assays and importance of immune complexes

Abstract

Given the morbidity and occasional mortality associated with cytomegalovirus infection and the requirement for good seroepidemiologic tools, assays of high sensitivity and reliability are needed for detection of cytomegalovirus-specific antibody. We report the successful application of two sensitive techniques, antibody-dependent cellular cytotoxicity (ADCC) and the enzyme-linked immunosorbent assay (ELISA) for the measurement of these antibodies and document their favorable comparison with conventional techniques, complement fixation (CF) and indirect hemagglutination (IHA). A coded panel of 48 sera from patients with culture-proven cytomegalovirus infection and disease controls was tested in a controlled fashion by all four procedures. Among 18 CF-positive sera, specific antibody was detected by IHA, ADCC and ELISA in dilutions 100 to 1000-fold higher than measurable by the CF test. Ten of 15 sera, seronegative by CF, were nevertheless found to be cytomegalovirus antibody-positive when assessed by the other procedures. Further, the importance of circulating antigen-antibody complexes upon ADCC test results was documented. Eight sera, known to be antibody-positive by other techniques but with an unexpectedly low (or negligible) capacity to induced ADCC, were found to be immune complex-positive by the Raji cell assay. Ultracentrifugation, useful in precipitating antigen-antibody complexes, enhanced ADCC activity in five of six sera known to be complex-positive. It is suggested that the simultaneous application of multiple antibody detection systems, particularly the newly-developed ones (ADCC, ELISA) will provide both earlier diagnostic information as well as a more comprehensive understanding of the human host's immune response to infection with cytomegalovirus.