The value of CMV IgG avidity and immunoblot for timing the onset of primary CMV infection in pregnancy

Enders, Gisela; Daiminger, Anja; Bäder, Ursula; Exler, Simone; Schimpf, Yvonne; Enders, Martin

doi:10.1016/j.jcv.2012.09.015

Cited by 46 publications

(21 citation statements)

References 21 publications

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“…Although this finding is consistent with published data (2,24), it raises questions about the utility of algorithms requiring CMV IgM reactivity as a criterion for CMV IgG avidity testing (12,13,24). This issue is addressed in a companion publication (26) in which we assess the potential impact of 4 different CMV IgM assays on a reflexive algorithm in which only IgM-positive samples are tested for IgG avidity.…”

Section: Discussionsupporting

confidence: 82%

“…This finding indicates that unacceptably low EIA sensitivity does not explain the unexpectedly large number of CMV IgG-negative specimens submitted for CMV IgG avidity testing. Rather, it suggests that these sera were not tested for CMV IgG before submission, an approach that is inconsistent with recommended algorithms for diagnosing and managing primary CMV infection during pregnancy (12,13,22,23). Programs are thus needed to educate physicians and laboratory personnel on the need to demonstrate CMV IgG positivity before submitting samples to an esoteric reference laboratory for CMV IgG avidity testing.…”

Section: Discussionmentioning

confidence: 99%

“…IgG avidity gradually matures over time, so that IgG detected by 5 to 6 months after a primary infection exhibits high avidity; thus, a low CMV IgG avidity result is a strong indicator of primary infection within the preceding 5 to 6 months (2,3,6,12,13). CMV IgG avidity is more accurate than CMV IgM detection for identifying primary infection, since CMV IgM persists for Ͼ6 months in some patients (2,7,14).…”

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confidence: 99%

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Performance of a Cytomegalovirus IgG Enzyme Immunoassay Kit Modified To Measure Avidity

Prince

Lapé-Nixon

Novak-Weekley³

2014

Clin Vaccine Immunol

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bThe measurement of cytomegalovirus (CMV) IgG avidity accurately discriminates recent and past CMV infections. We sought to determine if the Wampole Laboratories CMV IgG enzyme immunoassay (EIA) could be modified to measure avidity. The evaluation panel consisted of 156 serum samples we used in 2002 to validate a laboratory-developed EIA, in which 78 serum samples exhibited low avidity, 7 exhibited intermediate avidity, and 71 exhibited high avidity. The qualitative agreement between the two avidity assays was 94% (147/156); all 9 sera with discordant results exhibited intermediate avidity in one of the assays. The avidity index (AI) values in the two assays showed excellent correlation (r ‫؍‬ 0.96, P < 0.0001). The definition of high avidity was verified for the Wampole assay by demonstrating high avidity in 91/93 (98%) recently collected CMV IgG-positive/IgM-negative serum samples. The performance of the Wampole avidity assay in a reference laboratory setting was assessed using 470 consecutive serum samples submitted for CMV IgG avidity testing. Surprisingly, 101 serum samples were negative when screened for CMV IgG using the Wampole kit per the package insert; 98 of these 101 serum samples were tested using a CMV IgG chemiluminescent immunoassay, and only 5 were positive. Of the 369 CMV IgG-positive samples, 6% exhibited low IgG avidity, 6% exhibited intermediate avidity, and 88% exhibited high avidity; CMV IgM detection rates were inversely related to AI levels. These findings show that (i) the Wampole CMV IgG EIA can be modified to measure CMV IgG avidity, (ii) many samples are apparently submitted for avidity testing without knowledge of their CMV IgG status, and (iii) most CMV IgG-positive sera submitted for avidity testing exhibit high avidity. T he accurate discrimination of primary cytomegalovirus (CMV)infection from reactivation or reinfection plays an important role in the clinical management of pregnant women (1-5). Primary CMV infection during pregnancy may lead to intrauterine infection of the fetus, which is associated with hearing loss, blindness, and mental retardation (6-8). In contrast, CMV reactivation or reinfection during pregnancy is rarely associated with intrauterine fetal infection (2, 7). The accurate identification of primary CMV infection is also important in managing solid organ transplant recipients, who exhibit an increased risk of organ rejection following primary CMV infection (9-11).Over the last decade, the assessment of CMV IgG avidity has become the preferred laboratory tool for identifying patients with primary CMV infection (4, 5). IgG avidity gradually matures over time, so that IgG detected by 5 to 6 months after a primary infection exhibits high avidity; thus, a low CMV IgG avidity result is a strong indicator of primary infection within the preceding 5 to 6 months (2, 3, 6, 12, 13). CMV IgG avidity is more accurate than CMV IgM detection for identifying primary infection, since CMV IgM persists for Ͼ6 months in some patients (2,7,14).In 2002, we validated a laboratory...

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Section: Discussionsupporting

confidence: 82%

Section: Discussionmentioning

confidence: 99%

mentioning

confidence: 99%

See 1 more Smart Citation

Performance of a Cytomegalovirus IgG Enzyme Immunoassay Kit Modified To Measure Avidity

Prince

Lapé-Nixon

Novak-Weekley³

2014

Clin Vaccine Immunol

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“…The measurement of CMV IgG avidity has emerged as one of the most useful laboratory assays for identifying primary CMV infection; this assay also enables an estimation of the length of time that has elapsed since the infection occurred (5,6). IgG avidity, defined as the aggregate strength of IgG binding to multiple antigenic epitopes of a given protein, gradually increases with time, reaching "high" levels by 5 to 6 months after the primary infection (1,4,(7)(8)(9). Thus, a finding of low CMV IgG avidity in a pregnant patient, particularly during the second or third trimester, suggests that CMV infection may have occurred after conception, which carries an increased risk of fetal infection (2,7,10).…”

mentioning

confidence: 99%

“…To enable accurate and efficient identification of primary CMV infection in pregnant women, several investigators have recommended a testing algorithm that combines the good sensitivity of CMV IgM detection with the good sensitivity and specificity of CMV IgG avidity testing (5,8,9,12,13). Per this reflexive algorithm, serum from a patient found to be positive for CMV IgG is first tested for CMV IgM, and only those sera found to be IgM reactive are tested in a CMV IgG avidity assay.…”

mentioning

confidence: 99%

Potential Impact of Different Cytomegalovirus (CMV) IgM Assays on an Algorithm Requiring IgM Reactivity as a Criterion for Measuring CMV IgG Avidity

Prince

Lapé-Nixon

Brenner

et al. 2014

Clin Vaccine Immunol

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The measurement of cytomegalovirus (CMV) IgG avidity is a powerful tool for identifying individuals with recent CMV infection. Because such patients are expected to be positive for CMV IgM, several investigators have suggested that CMV IgG-positive sera first be screened for CMV IgM and then only the IgM-reactive sera be tested for avidity. We investigated the impact of different CMV IgM assays on such a reflexing algorithm using a panel of 369 were IgM negative by BIFA, 10 by ELFA, and 15 by EIA and CIA. In both these avidity groups, BIFA IgM-negative sera were also negative by the other 3 assays. These findings demonstrate that an algorithm requiring CMV IgM reactivity as a criterion for CMV IgG avidity testing does not identify all low-avidity sera and thus misses some cases of acute CMV infection.

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Prenatal diagnosis of congenital cytomegalovirus infection in 115 cases: a 5 years' single center experience

Enders¹,

Daiminger²,

Exler³

et al. 2017

Prenatal Diagnosis

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The value of CMV IgG avidity and immunoblot for timing the onset of primary CMV infection in pregnancy

Cited by 46 publications

References 21 publications

Performance of a Cytomegalovirus IgG Enzyme Immunoassay Kit Modified To Measure Avidity

Performance of a Cytomegalovirus IgG Enzyme Immunoassay Kit Modified To Measure Avidity

Potential Impact of Different Cytomegalovirus (CMV) IgM Assays on an Algorithm Requiring IgM Reactivity as a Criterion for Measuring CMV IgG Avidity

Prenatal diagnosis of congenital cytomegalovirus infection in 115 cases: a 5 years' single center experience

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