Kinetics of specific immunoglobulins M, E, A, and G in congenital, primary, and secondary cytomegalovirus infection studied by antibody-capture enzyme-linked immunosorbent assay

Abstract

Antibody-capture enzyme-linked immunosorbent assay (ELISA) using enzyme-labeled cytomegalovirus (CMV) nuclear antigen is a reliable and easily performed test suitable for routine use. As the serologic response to CMV infection may, however, vary considerably among patients, we have studied the kinetics of CMV-specific immunoglobulin M (IgM), IgE, IgA, and IgG antibodies in 352 sera from 61 patients by using antibody-capture ELISA and complement fixation (CF) tests. In a CMV mononucleosis group (n = 17), most patients had antibodies of all four immunoglobulin classes, but antibody levels decreased rapidly, with half the patients having a borderline-positive or a negative reaction for all classes, except IgG, 2 months after the appearance of symptoms. Twelve patients with a primary CMV infection after renal or bone marrow transplantation also developed all immunoglobulin-class antibodies. In only two patients did CMV IgM and IgE antibodies precede seroconversion of CF antibodies, and in one patient, these antibodies lagged months behind. Most patients had all classes of CMV antibodies, except IgA, for a year or more. Among 10 transplant patients with a secondary CMV infection, 50% had long-lasting IgM antibodies, and very few had IgE or IgA antibodies, but all had IgG antibodies to CMV. In 13 infected infants, the CMV-specific serologic response was also characterized by long-lasting IgM, IgE, and IgG antibodies. Two patients did not develop detectable IgM antibodies, and one of these did not show IgE antibodies either. The IgA response in infants as a whole was lacking; a few, however, were borderline positive. Of the nine acquired immunodeficiency syndrome patients with CMV infection studied during their last year of life, only one had antibodies in all four classes, the rest had only CF antibodies, and all except for one had IgG-class antibodies. All sera studied were also tested against a control antigen produced from noninfected cell nuclei. It was found that some patients developed antibodies to nuclear antigens in parallel with the rise in specific antibodies. The nonspecific antibodies occurred in all four classes, but most often they were of the IgM class. Addition of unlabeled control antigen to the conjugates was not always sufficient to abort this nonspecific reaction.