Study purpose: It is standard practice to test organ donors for CMV IgM as a marker of recent CMV infection (defined as primary infection within the preceding 3 months). However, extensive studies have shown that CMV IgM is not a reliable marker of recent CMV infection due to its persistence for >1 year following primary infection in around 25% of individuals. In contrast, CMV IgG avidity has been shown to be a highly sensitive and specific marker for distinguishing recent from non-recent CMV infection. Defined as the aggregate strength with which IgG molecules bind to antigen, CMV IgG avidity is low during the first 3 months following infection, and gradually matures to high by 6 months post-infection. Thus, high CMV IgG avidity in a CMV IgM-positive sample indicates non-recent, rather than recent, CMV infection. We sought to determine the CMV IgG avidity status of CMV IgM-positive serum specimens from heart-beating organ donors.

Methods: The CMV IgG avidity enzyme immunoassay (EIA) from Euroimmun (Lubeck, Germany) was used to test 39 CMV IgM-positive donor sera and 2 known low avidity sera obtained from a reference laboratory. In this assay, diluted serum is added to 2 microtiter wells coated with CMV antigens. After incubation, one well is washed with phosphate buffer and the other well is washed with phosphate buffer containing urea, a mild protein denaturant; conjugate, substrate, and stop reagents are then employed as in a routine EIA. Low avidity IgG remains attached to antigen in the presence of phosphate buffer, but dissociates from antigen in the presence of phosphate buffer containing urea. Results are expressed as an avidity index (AI) and interpreted qualitatively: AI <40% low avidity, 40%-60% intermediate avidity, >60% high avidity.

Results: Of 39 CMV IgM-positive donor samples, 37 exhibited high CMV IgG avidity, and 2 exhibited intermediate avidity; none of the samples exhibited low CMV IgG avidity. Both known low avidity sera also exhibited low avidity in the Euroimmun EIA, demonstrating that the assay functioned properly.

Conclusions: CMV IgG avidity testing indicated that the vast majority (37/39) of CMV IgM-positive donors were infected with CMV more than 6 months earlier, rather than within the preceding 3 months. If verified in larger studies, this finding suggests that CMV IgG avidity would be a better test than CMV IgM for identifying organ donors recently infected with CMV.

CITATION INFORMATION: Prince H, Nowicki M. Improving Donor Screening for Cytomegalovirus (CMV): Is CMV IgG Avidity Better Than CMV IgM? Am J Transplant. 2017;17 (suppl 3).

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