CMV IgG Avidity

Distinguishing between recent and past cytomegalovirus (CMV) infection can be difficult in transplant recipients and pregnant women. Almost everyone with recent CMV infection have increased levels of CMV IgM. CMV IgM detection is a sensitive marker of primary CMV infection, but its specificity is poor because CMV IgM is also produced during viral reactivation and persists following primary infection in some individuals.

Measurement of CMV IgG avidity can assist in discriminating recent from past CMV infection. IgG avidity is defined as the strength with which a mixture of polyclonal IgG molecules bind to multiple antigenic epitopes expressed by a protein. Avidity gradually matures during the 6 months following primary infection, reflecting the antigen-driven selection of B cells producing IgG of increasing affinity. IgG antibodies produced during the first few months following primary infection bind weakly to antigens and exhibit low avidity. In contrast, antibodies produced by 6 months post-infection bind tightly to antigens and exhibit high avidity. 

The basic methodology used to measure avidity capitalizes on the weak binding of low-avidity IgG to a mixture of CMV antigens. Antigen-bound low-avidity IgG, but not high-avidity IgG, dissociates from the antigen in the presence of mild protein denaturants, such as urea, potassium thiocyanate, and guanidine chloride. The most common test format is an enzyme-linked immunosorbent assay (ELISA) utilizing urea as the dissociating agent.

A low CMV IgG avidity is a reliable indicator of CMV infection within the previous 3 to 4 months, whereas  a high avidity index essentially excludes the primary infection within that timeframe. 

The reference interval for defining low avidity is typically 0.5 or less, whereas the AI cutoff point for defining high avidity is 0.6 or greater. Values of 0.51to 0.59 are considered intermediate avidity.

Specimen requirement is 0.5 mL of serum. 

Reference

Prince HE, Lape-Nixon, M. Role of Cytomegalovirus (CMV) IgG Avidity Testing in Diagnosing Primary CMV Infection during Pregnancy, Clin Vaccine Immunol, 2014;21(10):1377-1384.