Clinical Evaluation of a Chemiluminescence Immunoassay for Determination of Immunoglobulin G Avidity to Human Cytomegalovirus

Abstract

Clinical evaluation of a novel fully automated chemiluminescence immunoassay for determination of immunoglobulin G avidity to human cytomegalovirus (HCMV) showed 92.8% sensitivity and 84.7% specificity in detecting a recent (<90 days) primary HCMV infection. The assay appears useful for accurately diagnosing recent primary HCMV infections.Human cytomegalovirus (HCMV) is the leading infectious agent causing mental retardation and deafness in newborns (14). Since symptomatic congenital infections are mostly due to intrauterine transmission following primary maternal infection (4), differential diagnosis of primary versus recurrent infection (or persistence of HCMV-specific immunoglobulin M [IgM] antibody) is crucial for correct counseling and management of pregnancy. The determination of IgG avidity has been shown to help in distinguishing primary from nonprimary HCMV infection (1,8,10), as low avidity values have been shown to be associated to recent primary HCMV infections. Indeed, determination of IgG avidity has become a key step in the algorithm for the interpretation of a positive IgM result in pregnant women (10).The aim of the study was the clinical evaluation of a fully automated chemiluminescence immunoassay for the determination of HCMV-specific IgG avidity (Liaison CMV IgG avidity assay) developed by DiaSorin, Saluggia, Italy.For this purpose, 413 sera obtained from 212 subjects were examined. The sera had been characterized previously and divided into the following groups: group A, including 167 sequential serum samples from 78 patients collected Յ90 (n ϭ 112), 91 to 180 (n ϭ 38), and Ͼ180 (n ϭ 17) days after the onset of primary HCMV infection; group B, including 56 serum samples from 17 pregnant women with persistent HCMVspecific IgM antibody; group C, including 87 sequential serum samples from 14 solid organ transplant recipients with recurrent HCMV infection; and group D, including 103 HCMV IgG-positive, IgM-negative serum samples from 49 pregnant women and 54 transplanted patients with past HCMV infection.Diagnosis of primary HCMV infection was based on the following criteria: seroconversion, decreasing levels of HCMVspecific IgM antibody, increasing levels of IgG antibody avidity, and detection of HCMV and HCMV products in blood. Dating of the onset was based on the presence of abnormal laboratory findings and/or clinical symptoms (10). Persistent IgM antibody was defined as stable IgM values for Ն3 months in the absence of serologic, virologic, or clinical data indicative of a recent primary HCMV infection in the mothers and of congenital infection in the relevant newborn babies. Congenital HCMV infection was diagnosed within the first 2 weeks of life by virus isolation from urine and virus detection in blood (7,12). Recurrent HCMV infection in transplanted patients was diagnosed by quantitative determination of pp65 antigenemia in peripheral blood leukocytes (5).Sera examined in the present study had been previously characterized for HCMV-specific IgG and IgM antibody by in-house-developed enz...

Role of Cytomegalovirus (CMV) IgG Avidity Testing in Diagnosing Primary CMV Infection during Pregnancy

“…A reflexive algorithm requiring IgG avidity testing only on IgM-positive samples will thus miss a small number of primary infections. For this reason, some investigators recommend that all sera first be tested for CMV IgG and IgM and that all IgG-positive samples then be tested for CMV IgG avidity, regardless of the IgM result (5,36,50,57). In addition to identifying IgM-negative patients with low IgG avidity, this approach also detects the small number of patients with an IgGnegative, IgM-positive result set, indicative of very recent CMV infection; seroconversion should be documented to ensure that the IgM result is a true positive.…”

“…These interpretive criteria have now been adopted by the manufacturer (bioMérieux). The Liaison assay (DiaSorin) appeared soon after the Vidas assay, and evaluation data were published by the Pavia group in 2004 (50). At the manufacturer's suggested diagnostic AI threshold of 20%, the Liaison assay correctly identified 93% of primary infections and 85% of past infections.…”

Development of Fully Automated Determination of Marker-Specific Immunoglobulin G (IgG) Avidity Based on the Avidity Competition Assay Format: Application for Abbott Architect Cytomegalovirus and Toxo IgG Avidity Assays

“…Accordingly, some assays utilize specific IgG concentration-dependent manual endpoint titration, while others only employ fixed dilution factors independent of the marker-specific IgG level (1,9,21). The AVIcomp assays rely on a number of dilution protocols that are automatically selected based on the concentration of marker-specific IgG.…”

Cytomegalovirus pneumonia in immunocompetent host: Case report and literature review

“…CF for CMV showed a fourfold increase (1:160). The avidity test for CMV 12 showed a low titer of 0.042 (low titer < 0.20; high titer > 0.30), confirming primary CMV infection.…”