Evaluation of an in-house specific immunoglobulin G (IgG) avidity ELISA for distinguishing recent primary from long-term human cytomegalovirus (HCMV) infection

Souza, Silmara de; Bonon, Sandra Helena Alves; Costa, Sandra Cecı́lia Botelho; Rossi, Claudio

doi:10.1590/s0036-46652003000600005

Cited by 14 publications

(14 citation statements)

References 24 publications

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“…Other avidity cutoff values analyzed were 0.7 (Ն0.7, high avidity suggestive of past infection; Ͻ0.7, low avidity suggestive of recent infection) (1, 3); and 0.6 (Ն0.6, high avidity suggestive of past infection; Ͻ0.6, low avidity suggestive of recent infection). Cutoff values recommended by the manufacturer of Ն0.8 for high avidity, Ͻ0.8 to 0.2 for intermediate (indeterminate) avidity, and Ͻ0.2 for low avidity were not analyzed because most of the test range assigns indeterminate avidity and because the Ͻ0.2 cutoff has been shown to be too low to identify many sera from acute CMV infection (1,3,6,7,23).…”

Section: Methodsmentioning

confidence: 99%

National Prevalence Estimates for Cytomegalovirus IgM and IgG Avidity and Association between High IgM Antibody Titer and Low IgG Avidity

Dollard

Staras

Amin

et al. 2011

Clin Vaccine Immunol

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Primary cytomegalovirus (CMV) infection of the mother during pregnancy presents risk of CMV infection of the fetus with resulting permanent disability. CMV IgM antibody is generated following primary CMV infection but also can appear during nonprimary CMV infection and is thus of limited diagnostic use by itself. In contrast, the presence of low CMV IgG avidity has been shown to be a unique and reliable serologic indicator of primary CMV infection. We measured CMV IgG and IgM antibody levels and IgG avidity in sera from a population sample of 6,067 U.S. women aged 12 to 49 years from NHANES (National Health and Nutrition Examination Survey). The CMV IgG prevalence was 58% overall and increased strongly with age. The CMV IgM prevalence was 3.0% overall and remained relatively flat across age groups. The prevalence of low IgG avidity was 2.0% overall, decreased sharply with age, and was seen mainly among IgM-positive sera. Fourteen to 18% of the CMV IgM-positive sera were low IgG avidity, presumably representing primary CMV infection. High CMV IgM antibody titer was a strong predictor of low IgG avidity. The ability to reliably identify primary CMV infection during pregnancy is important for management of the pregnancy, including possible treatment options for the fetus. Both IgM and IgG avidity measurements provide useful clinical information for evaluating primary CMV infection, although commercial tests for CMV IgG avidity are not yet widely available in the United States.

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Section: Methodsmentioning

confidence: 99%

National Prevalence Estimates for Cytomegalovirus IgM and IgG Avidity and Association between High IgM Antibody Titer and Low IgG Avidity

Dollard

Staras

Amin

et al. 2011

Clin Vaccine Immunol

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“…The other 3 groups modified a CMV IgG kit to include a urea buffer wash step; the Brussels and Paris groups employed 8 M urea, whereas the Stuttgart group used 6 M urea. Other investigators have taken the latter approach of modifying CMV IgG kits from different manufacturers and typically employ 6 M urea (16,17,20,22,41,42). Table 2 lists the currently available CMV IgG avidity assays known to the authors.…”

Section: Commercially Available CMV Igg Avidity Assaysmentioning

confidence: 99%

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

Prince

Lapé-Nixon

2014

Clin Vaccine Immunol

173

141

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The risk of intrauterine transmission of cytomegalovirus (CMV) during pregnancy is much greater for women who contract primary CMV infection after conception than for women with evidence of infection (circulating CMV antibodies) before conception. Thus, laboratory tests that aid in the identification of recent primary CMV infection are important tools for managing the care of pregnant women suspected of having been exposed to CMV. 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. Studies conducted over the last 20 years convincingly demonstrate that measurement of CMV IgG avidity is both a sensitive and a specific method for identifying pregnant women with recent primary CMV infection and thus at increased risk for vertical CMV transmission. IgG avidity is defined as the strength with which IgG binds to antigenic epitopes expressed by a given protein; it matures gradually during the 6 months following primary infection. Low CMV IgG avidity is an accurate indicator of primary infection within the preceding 3 to 4 months, whereas high avidity excludes primary infection within the preceding 3 months. In this minireview, we summarize published data demonstrating the clinical utility of CMV IgG avidity results for estimating time since primary infection in pregnant women, describe commercially available CMV IgG avidity assays, and discuss some of the issues and controversies surrounding CMV IgG avidity testing during pregnancy. C ongenital cytomegalovirus (CMV) infection is the most common intrauterine infection, occurring in approximately 40,000 newborns each year in the United States (1-4). The clinical manifestations include sensorineural hearing loss, visual impairment, mental retardation, and cognitive defects; 4% of infected infants do not survive (1,2,5,6).Several studies have demonstrated a strong link between primary CMV infection of the mother and in utero CMV transmission. The risk of congenital infection is approximately 40% in babies born to mothers who acquire a primary (initial) CMV infection after conception; in contrast, the risk is only about 1% in infants born to mothers who have evidence of CMV infection (i.e., circulating CMV antibodies) before conception (1,3,(6)(7)(8)(9). The few cases of CMV transmission in seropositive mothers reflect nonprimary CMV infections, defined as either viral reactivation or infection with a different strain of CMV during pregnancy (2, 3, 5). Preexisting maternal antibodies thus appear to offer substantial protection against congenital infection, most likely due to the ability of antibodies to control viremia (2, 9, 10).The established link between primary CMV infection during pregnancy and congenital infection makes identification of primary CMV infection an important goal in maternal and neonatal health care. However, Ͼ95% of pregnant women with primary CMV infection are asymptomatic and thus cannot be ...

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“…We concluded that the pregnant woman had thus been infected before conception. Some authors suggested that the CMV-IgG avidity assay might help distinguish primary from recurrent infection and/or exclude the risk of congenital CMV infection [ 2 ]; however, it was not used in the present case. It has been suggested that symptomatic congenital infection is rare in infants of women with preconceptional immunity.…”

Section: Discussionmentioning

confidence: 93%

Congenital cytomegalovirus infection after maternal persistent immunoglobulin-M antibodies against cytomegalovirus prior to conception

Nakajima

Masaoka

Yamamoto

2013

Case Reports in Perinatal Medicine

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We describe a case of congenital cytomegalovirus (CMV) infection transmitted by an immunocompetent woman infected before conception with continuous hyper CMV-immunoglobulin M (IgM). A 33-year-old woman whose CMV-IgM levels were stable more than 8 months before conception was referred at 35 gestational weeks due to fetal unilateral cerebral ventriculomegaly. The maternal serum CMV-IgG was 61.7 U/mL, and the CMV-IgM was 3.89 U/mL. An infant girl weighing 2297 g was delivered transvaginally. The neonate was found to have congenital CMV infection. After delivery, the high maternal CMV-IgM level has continued for more than 2 years. In conclusion, although continuous hyper CMV-IgM is rare, the infants of infected women may develop congenital infection. It is our hope that the information provided in the present case will further aid clinicians in counseling patients who find themselves in this situation.

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Evaluation of an in-house specific immunoglobulin G (IgG) avidity ELISA for distinguishing recent primary from long-term human cytomegalovirus (HCMV) infection

Cited by 14 publications

References 24 publications

National Prevalence Estimates for Cytomegalovirus IgM and IgG Avidity and Association between High IgM Antibody Titer and Low IgG Avidity

National Prevalence Estimates for Cytomegalovirus IgM and IgG Avidity and Association between High IgM Antibody Titer and Low IgG Avidity

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

Congenital cytomegalovirus infection after maternal persistent immunoglobulin-M antibodies against cytomegalovirus prior to conception

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