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Analytical issues possibly affecting the performance of commercial human cytomegalovirus IgG avidity assays
M Berth1, L Grangeot-Keros, F Heskia
1Immunology Department, Algemeen Medisch Laboratorium (AML), Emiel Vloorsstraat 9, 2020, Antwerpen, Belgium, mario.berth@aml-lab.be.
Insights
Low cytomegalovirus (CMV) immunoglobulin G (IgG) avidity indexes are rare but can occur in samples with very low IgG levels. Caution is advised when interpreting CMV IgG avidity in such cases, regardless of the assay used.
Area of Science:
- Clinical diagnostics
- Immunology
- Virology
Background:
- Cytomegalovirus (CMV) immunoglobulin G (IgG) avidity assays are crucial for diagnosing past infections.
- Occasionally, very low IgG levels can lead to inappropriately low avidity indexes, posing diagnostic challenges.
- Understanding the causes and clinical significance of these low avidity indexes is essential.
Purpose of the Study:
- To investigate the causes and clinical importance of inappropriately low CMV IgG avidity indexes.
- To compare the performance of different CMV IgG avidity assays in samples with low IgG levels.
- To assess the impact of chaotropic agents on avidity index determination.
Main Methods:
- Comparison of three commercial CMV IgG avidity assays (VIDAS, Liaison, Architect) on 129 patient samples with past CMV infections.
- Focus on samples exhibiting low CMV IgG levels.
- Further evaluation of low avidity samples using seven different urea-based IgG avidity assays.
Main Results:
- Inappropriately low CMV IgG avidity indexes were confirmed to occur rarely in samples with very low IgG levels.
- The phenomenon is assay-independent, affecting multiple commercial kits.
- Assays utilizing chaotropic agents demonstrated a more frequent and pronounced effect.
Conclusions:
- Very low CMV IgG levels can lead to unreliable avidity index results, though this is uncommon.
- The choice of assay, particularly those using chaotropic agents, can influence the observed avidity index.
- Interpretation of CMV IgG avidity in immunoglobulin M (IgM)-negative samples with very low IgG levels requires caution, irrespective of the assay method.
Abstract:
In the majority of cytomegalovirus (CMV) immunoglobulin G (IgG) avidity assays, avidity determination can be performed on the entire CMV IgG measurable positive concentration range. However, in some exceptional samples with very low IgG levels, inappropriately low avidity indexes have been described. In this study, we addressed some possible causes and the clinical importance of these inappropriately low avidity indexes. We compared VIDAS (bioMérieux), Liaison (DiaSorin), and Architect (Abbott) CMV IgG avidity assays on 129 samples from patients with past CMV infections, focusing on samples with low IgG levels. Inappropriately low avidity samples were further evaluated using seven different urea-based IgG avidity assays. We confirmed that inappropriately low avidity indexes in samples with very low IgG levels occur, but are rare. We could show that this phenomenon is not confined to a single assay and that assays employing chaotropic agents are affected more frequently and profoundly. In situations where the CMV IgG avidity is performed on CMV immunoglobulin M (IgM)-negative samples, the avidity index should be interpreted cautiously in cases of very low CMV IgG levels, whatever the technique used.
