Clinical evaluation of new automated cytomegalovirus IgM and IgG assays for the Elecsys® analyser platform

Abstract

Cytomegalovirus (CMV) is a leading cause of physical and neurological abnormalities in newborns. Hence, the diagnosis of CMV infection in pregnant women is necessary in order to allow appropriate management of their pregnancy. New assays have been developed for the Roche Elecsys® immunoassay platform that detect CMV-specific immunoglobulin (Ig)M and IgG, with the IgM assay designed to target IgM produced at the start of infection rather than IgM persisting later in infection. This study aimed to evaluate the performance of the new assays compared with other commercial kits widely distributed in laboratories. The performance of the Elecsys and comparator CMV IgM and IgG assays was assessed using 967 preselected patient samples characterised by CMV infection status, as well as being compared using 1,668 unselected clinical samples. The Elecsys CMV IgM and IgG assays performed consistently with comparator assays using the preselected samples. The Elecsys CMV IgM assay showed improved sensitivity compared with the Enzygnost® assay in primary infection (91.2 % vs. 79.4 %) and improved specificity over the Architect® assay in potentially cross-reacting samples (94.1 % vs. 82.4 %). The Elecsys IgM assay reported fewer positive results in the later stages of CMV infection compared with ETI-CYTOK-M ELISA, while the Elecsys IgG assay reported slightly fewer negative results in the early stages of infection compared with ETI-CYTOK-G ELISA. There was good agreement between Elecsys and comparator assays using unselected clinical samples (range 90.4-99.4 %). The Elecsys CMV IgM and IgG assays compare well with routinely used assays and are suitable for clinical use.

Detection of Cytomegalovirus Antibodies Using a Biosensor Based on Imaging Ellipsometry

“…However, the identification of antibody types may help to determine the course of disease, and BIE may be used as a clinical primary screening tool for CMV patients. IgM is produced in large amounts early in infection (reaching a peak in the first month), and is followed by IgG production [ 7 , 31 ]. Levels of IgM decline in the months following the onset of infection, whereas IgG levels persist for the rest of the patient’s life [ 32 , 33 ].…”

“…For instance, the CMV immunoglobulin G (IgG) avidity assay can help to distinguish primary from non-primary human CMV infections [ 3 – 5 ]. The key immune methods used for CMV antibody detection are: enzyme-linked immunosorbent assay (ELISA) [ 6 ], Elecsys [ 7 ], electrochemiluminescence immunoassay (ECLIA) [ 8 ], immunofluorescence assay (IFA) [ 9 ], flow cytometry (FCM) [ 10 ] and immunoblots [ 11 ]. Additionally, new immune methods for CMV antibody detection have been developed, such as the chemiluminesent microparticle immunoassay (CMIA) [ 12 ] and protein microarrays [ 13 , 14 ].…”

Advocating for cytomegalovirus maternal serologic screening in the first trimester of pregnancy: if you do not know where you are going, you will wind up somewhere else

“…IgM and IgG avidity assays available on new high throughput automated platforms have high sensitivity to diagnose primary infection. [7][8][9]16 Albeit some remaining pitfalls such as the interpretation of virological profile in serum with a low level of IgG, the tools available for the diagnosis of maternal primary infection are reliable. 10,11 The evaluation of the 4 most used CMV IgM assays in Europe reported that the mean sensitivity to diagnose a primary infection in the first trimester of pregnancy was 93.5% (range, 79.4%−98.0%).…”

Is it time for routine prenatal serological screening for congenital cytomegalovirus?

“…• We propose an algorithm for the management of CMV primary infection in pregnancy. [19][20][21][22] Albeit some remaining pitfalls such as the interpretation of virological profile in serum with low level of IgG, the tools available for the diagnosis of maternal primary infection are reliable. 23,24 Maternal non-primary infection cannot be diagnosed by serology 25,26 and there are no other validated markers to identify seropositive pregnant women at risk of fetal transmission.…”

“…IgM and IgG avidity assays available on new high throughput automated platforms have high sensitivity to diagnose primary infection 19‐22 . Albeit some remaining pitfalls such as the interpretation of virological profile in serum with low level of IgG, the tools available for the diagnosis of maternal primary infection are reliable 23,24 …”