Journal of Clinical Virology 72 (2015) 46–48

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Journal of Clinical Virology

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Short communication

Comparison of the LIAISON® CMV IgG Avidity II and the VIDAS® CMV
IgG Avidity II assays for the diagnosis of primary infection in pregnant
women
Yann Sellier a,b , Tiffany Guilleminot a,c , Yves Ville a,b , Marianne Leruez-Ville a,c,∗
a
EA 73-28, Université Paris Descartes, Sorbonne Paris Cité, France
b
AP-HP, Maternité et Unité de Médecine Foetale, Hôpital Necker-E.M., Paris 75015, France
c
AP-HP, Laboratoire de Microbiologie Clinique, Hôpital Necker-E.M., National Reference Center for Cytomegalovirus-Associated Laboratory, Paris 75015,
France

a r t i c l e i n f o a b s t r a c t

Article history: Background: The accuracy of IgG avidity assays is crucial for the diagnosis of primary CMV infection in
Received 23 June 2015 pregnancy.
Received in revised form 27 August 2015 Objective: To compare the performance of the second generation avidity assays LIAISON® CMV IgG Avidity
Accepted 31 August 2015
II and VIDAS® CMV IgG Avidity II for the diagnosis of primary infection in pregnant women.
Study design: In our laboratory, in sera of pregnant women presenting with positive CMV IgG and positive
Keywords:
CMV IgM, the two avidity assays were run in parallel from January 2013 to April 2015.
Cytomegalovirus
Results: The results of the 2 avidity assays were analyzed in 280 sera. The correlation between the second
IgG avidity
LIAISON
generation LIAISON® and VIDAS® avidity results was significantly higher than between the results of
VIDAS the first generation assays (77% versus 49%, p < 0.001). Discrepant results were mainly explained by the
Primary infection difficulty of the VIDAS® assay to reach intermediate and high avidity status over time, suggesting the
superiority of the LIAISON® assay to achieve high avidity levels. In 4 sera from 3 pregnant women (1.4%)
with documented primary infection the LIAISON® avidity was falsely high. In these cases the level of CMV
IgG was low (<50 U/mL).
Conclusion: The LIAISON® CMV IgG Avidity II assay reached more rapidly higher avidity status than the
VIDAS® CMV IgG Avidity II. However, with the LIAISON® CMV IgG Avidity II, we identified rare sera with
high positive avidity values in documented recent seroconversion. The advantages and drawbacks of each
assay must be known for a sound interpretation of the results.
© 2015 Elsevier B.V. All rights reserved.

1. Background mission [4–6]. Discordance between avidity commercial kits have

Although systematic CMV screening is not recommended in
France, CMV serology is frequently performed in the first trimester
of pregnancy. When IgG and IgM antibodies are detected, CMV IgG
avidity index is used to discriminate between primary infection
during or prior to pregnancy based upon the correlation between
increased binding avidity of maternal IgG to CMV antigens over
time [1–3]. The accuracy of primary infection is crucial to evaluate
the risk of fetal transmission and to target women who could be
included in clinical trials evaluating the efficacy of treatment with
valacyclovir or hyper-immune immunoglobulin to limit fetal trans-
∗ Corresponding author at: Hospital Necker-Enfants-malades, 149 rue de Sèvres,
Paris 75015, France. Fax: + 33 1 44 49 49 60.
E-mail address: marianne.leruez@nck.aphp.fr (M. Leruez-Ville).
been reported in the literature [7–10], we use 2 different avidity
assays in parallel in our laboratory to determine the occurrence of
primary infection during pregnancy. In a previous study, we com-
pared the first generation of CMV IgG avidity assays proposed by
Diasorin (LIAISON® CMV IgG Avidity) and by BioMerieux (VIDAS®
CMV IgG Avidity) and found that the concordance between these
avidity tests (high, intermediate and low avidity) was only 49.5%
[9]. This discrepancy was mainly due to the fact that fewer sera
reached the high avidity status with the VIDAS® assay than with
the LIAISON® assay, suggesting that the cut-off values used in the
former test were too high. Both manufacturers have since upgraded
theirs CMV avidity assays and we have used these second genera-
tion assays in parallel in our laboratory since January 2013 [11].

http://dx.doi.org/10.1016/j.jcv.2015.08.018
1386-6532/© 2015 Elsevier B.V. All rights reserved.
 Y. Sellier et al. / Journal of Clinical Virology 72 (2015) 46–48 47

Table 1
Comparison of IgG avidity index interpretation (low, intermediate, high) with the 2 commercial assays in 280 sera from with CMV IgM positive or equivocal results.

N = 280 Avidity II Vidas BioMerieux

Low (<0.40) Intermediate (≥0.40 <0.65) High ≥ 0.65

Avidity II Liaison XL
Low (<0.150) 49 6 0
Intermediate (≥0.150 <0.250) 16 35 3
High ≥ 0.250 8 30 133
78% concordant interpretations
32% discordant interpretations

Table 2
Details of the virological profile of the 5 cases with sera presenting with low or non-interpretable VIDAS® CMV avidity and high LIAISON® CMV avidity.

Cases No. Week of IgG II Liaison IgM Liaison XL Avidity II IgG Vidas Avidity II Vidas CMV PCR In Transmission
pregnancy XL U/mL U/mL Liaison XL UA/mL blood in cp/mL du fœtus
and/or
newborna

1 12 <5 <5 ND ND ND ND
20 29 84 0.466 <6 ND 2700 Yes

2 18 6.5 <5 ND ND ND ND
23 40 26 0.811 <6 ND ND
24 50 48 0.822 <6 ND ND No

3 17 22 >140 0.317 5 ND 11300 Yes

4 14 31 50 0.314 12 0.25 ND
26 48 37 0.305 14 0.38 ND Yes

5 4 11.5 49 ND 8 0.32 6900

12 80 29 0.295 17 0.37 ND
16 69 22 0.439 12 0.39 ND No

ND = not done.
a
Documented by a positive CMV PCR in amniotic fluid and/or in neonatal saliva.

2. Objective The comparison of the results showed that the concordance

The objective of this study was to compare the results obtained
with the LIAISON® CMV IgG Avidity II (DiaSorin, Antony, France)
and the VIDAS® CMV IgG Avidity II (BioMérieux, Marcy L’Etoile,
France).
2.1. Study design
CMV IgG and CMV IgM were performed on the Liaison XL plat-
form with LIAISON® CMV IgG II and LIAISON® CMV IgM. When IgG
were positive (>14 U/mL) and IgM were equivocal (≥18 U/mL and
<22 U/mL) or positive (≥22 U/mL), CMV IgG avidity was tested with
both the LIAISON® and the VIDAS® avidity assays. The results were
interpreted as recommended by the manufacturer. A LIAISON®
CMV IgG Avidity II test below 0.150 indicates a primary infection in
the last 3 months, an index above 0.250 excludes a primary infec-
tion in the last 3 months and an index ranging from 0.150 to 0.250
is considered as intermediate. Similarly, a VIDAS® CMV IgG avid-
ity II index below 0.40 indicates a primary infection in the last 3
months, an index above 0.65 excludes a primary infection in the
last 3 months and an index ranging from 0.40 to 0.65 is considered
as intermediate. CMV DNA load in blood was assessed by a quanti-
tative CMV real time PCR (CMV-R gene, Argene, BioMerieux). Fetal
infection was confirmed by the detection of CMV DNA in amni-
otic fluid or in neonatal saliva samples. Comparison between the
correlations of avidity results was done by Chi2 analysis.
3. Results
Between January 2013 and April 2015, 280 sera from pregnant
women were found with positive CMV IgG and positive or equivocal
CMV IgM and both avidity tests were therefore performed.
between the interpretations of avidity assays was 77% (Table 1). The
correlation between the results of the second generation LIAISON®
and VIDAS® avidity assays was significantly higher than between
the results of the first generation assays (77% versus 49%, p < 0.001).
Among the 280 sera tested, there were 8 from 5 pregnant
women with a high avidity value obtained with the LIAISON® assay
and with a low or non-interpretable avidity (because of a negative
IgG value) with the VIDAS® assay. To better understand these cases,
previous or subsequent sera from these 5 women were also studied
when available (Table 2). In cases 1 and 2, seroconversion was iden-
tified to have occurred less than 3 months before (5 and 8 weeks
before respectively), in case 3 we could not obtain an earlier serum
sample but the virological profile of this case was in favour of a
recent primary infection with high IgM value and high CMV DNA
load in maternal blood.
In case 4, the avidity was high with the LIAISON® assay and
low with the VIDAS® assay at 14 weeks of pregnancy, no earlier
serum was available but on subsequent sera obtained at 26 weeks
of pregnancy, therefore more than 3 months after the first one, the
avidity with the VIDAS® assay remained low while the avidity with
the LIAISON® assay was high as could be expected after 3 months.
Although in the absence of a previous serum, one cannot be certain
which test gave a correct result at 14 weeks, the VIDAS® result in
the second sample is obviously misleading as the primary infection
happened more than 3 months before. In case 5, seroconversion
happened at around 4 weeks of pregnancy, 2 and 3 months later
the LIAISON® avidity values were already high while the VIDAS®
avidity values were still low.
4. Discussion
The correlation between the second generation LIAISON® and
VIDAS® avidity assays is significantly better than the correlation
48 Y. Sellier et al. / Journal of Clinical Virology 72 (2015) 46–48
described between first generation assays (p < 0.001). However,
most of the discrepant results (81%) between the 2 tests were due
to the fact that fewer sera reached the intermediate avidity status
or the high avidity status with the VIDAS® CMV IgG Avidity II assay
than with the LIAISON® CMV IgG Avidity II assay, suggesting that
the cut-off values used in the former test are probably still too high.
Lumley et al. have also recently underlined the superiority of the
LIAISON® assay to achieve high avidity levels. In their work, the per-
sistence of low IgG avidity over more than 3 months after primary
infection was reported in 9% of sera with the ARCHITECT CMV IgG
Avidity assay while the LIAISON® assay was able to generate high
avidity values in due time [10].
The highly discrepant results (low VIDAS® Avidity contrasting
with high LIAISON® avidity) obtained in 5 cases have two different
explanations. In 2 cases the discrepant results were due to persist-
ing low avidity over 3 months with the VIDAS® assay while the
LIAISON® assay was able to detect IgG maturation. In another 3
cases, the LIAISON® avidity values were obvious falsely high which
could have led to miss 3 true cases of primary infections (with fetal
transmission in 2 cases) if no other tests would have been per-
formed. These 3 cases were recent primary infections with low IgG
value (between 22 and 50 U/mL). Berth et al. also reported analyti-
cal issues affecting the performance of avidity index in cases of low
CMV IgG levels. However, in their study, in contrast with ours, rare
cases of falsely low avidity values were found in sera from immune
subjects with low levels of IgG and negative IgM [12].
In conclusion, this comparative study of the second-generation
avidity assays LIAISON® and VIDAS® showed encouraging results
with improved correlation between tests. The LIAISON® CMV IgG
Avidity II assay reached high avidity status more rapidly than the
Vidas assay. However, we identified a previously undescribed pit-
fall of this assay since in 3 pregnant women with ongoing primary
infections; the LIAISON® CMV IgG Avidity II assay gave falsely high
positive values. These limits do not challenge the usefulness of avid-
ity assays for the diagnosis of CMV primary infection in pregnancy
but they emphasise the need for caution in the interpretation of the
results particularly when the IgG value are low.
Funding
None.
Ethical approval
Not required.
Competing interest
MLV declare having received travel grants and honoraria for
speaking or participation at meetings or for reviewing scientific
project from DiaSorin and from BioMerieux. Others authors declare
no competing interests relevant to this work.
Acknowledgments
We thank the mid-wives from the Obstetric and Fetal medicine
department and the technicians of the Virology Laboratory for their
daily work on congenital CMV screening.
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