Avidity of immunoglobulin G directed against human cytomegalovirus during primary and secondary infections in immunocompetent and immunocompromised subjects

Abstract

Diagnosis of primary human cytomegalovirus (HCMV) infection is accomplished exclusively by serologic testing. Among the possible methods, the determination of immunoglobulin G (IgG) avidity is one of the least explored. In this work, we used a commercially available kit to test anti-HCMV IgG avidity in 336 serum samples from pregnant women and transplant recipients undergoing virologically proven HCMV primary or nonprimary infections and from latently infected blood donors. Our results demonstrate that the anti-HCMV IgG avidity test differentiates primary from nonprimary HCMV infections in both pregnant women and solid organ transplant recipients. In fact, 88.6% of primary infections and no secondary infections showed lowavidity IgG to HCMV. In particular, low IgG avidity is a marker of primary infection for 18 to 20 weeks after onset of symptoms in both immunocompromised and immunocompetent subjects.

Combination of microneutralization and avidity assays: Improved diagnosis of recent primary human cytomegalovirus infection in single serum sample of second trimester pregnancy

“…In consecutive serum samples of pregnant women with well-documented seroconversion ( Table I) the antibody response had matured to be of high avidity within an average of 22 weeks (17-30 weeks). This observation is in accordance to the data of Lazzarotto et al, [1997] who reported the appearance of high avidity index in transplant recipients after approximately 25 weeks and in pregnant women after 18-20 weeks. As presented in Table III with the combined application of the microneutralization assay and avidity assay all women who gave birth to congenitally infected infants were shown to have a primary infection.…”

“…Therefore, an alternative approach is necessary to ensure the identification of all congenital HCMV infections. Another serological method for identifying primary infection is the determination of IgG avidity [Blackburn et al, 1991;Lazzarotto et al, 1997;Grangeot-Keros et al, 1997;Bodeus et al, 1998;Bodeus and Goubau, 1999;Lazzarotto et al,1999]. One of the drawbacks of this assay, however, is that for calculation of the avidity index a minimum IgG concentration of 1000 PEI U/l is necessary.…”

“…A low positive NT titer in the presence of specific IgM antibodies, however, still represents a diagnostic problem especially if blood sampling occurred after the 12th week of gestation. To overcome this problem the combination of microneutralization test and another serological method was evaluated that has been shown to be useful for identifying primary HCMV infection: the IgG avidity test [Blackburn et al, 1991;Lazzarotto et al, 1997;Grangeot-Keros et al, 1997;Bodeus et al, 1998;Bodeus and Goubau, 1999;Lazzarotto et al, 1999]. In the present study the maturation kinetics of CMV-specific IgG avidity after IgG or NT seroconversion were investigated as well as the capacity of the avidity assay to differentiate primary from nonprimary infection in a single serum taken from women during the second trimester of pregnancy.…”

Laboratory signs of acute or recent cytomegalovirus infection are common in cirrhosis of the liver

“…On the other hand, in 19 IgM-negative patients with cirrhosis qPCR gave a positive result. This can be due to the fact that only 70% of non primary CMV infections are accompanied by the production of detectable levels of anti-CMV specific IgM [Nielsen et al, 1987;Lazzarotto et al, 1997].…”

“…The determination of IgG avidity, a useful procedure in discriminating primary versus recurrent infections [Lazzarotto et al, 1997], was carried out using a commercial kit (Cytomegalovirus IgG avidity EIA WELL; RADIM, Rome, Italy) based on the difference between the absorbance values due to antibody binding in the absence and presence of 4.5M urea. The test was conducted and the results interpreted as suggested by the manufacturers.…”