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Published on: November 29, 2019
Discrepancies between qualitative and quantitative analysis of cerebrospinal fluid IgG: densitometric comparison of
Geoffrey Keir1, Susana Barrio, Edward J Thompson
1Department of Neuroinflammation, Institute of Neurology, Queen Square, London WC1 N 3BG, UK.
Insights
Detecting local IgG synthesis in the central nervous system is crucial for diagnosing inflammatory brain diseases. Discrepancies between silver stain and IgG stain methods highlight the need for improved diagnostic techniques for cerebrospinal fluid (CSF) IgG.
Area of Science:
- Neurology
- Immunology
- Biochemistry
Background:
- Accurate detection of local immunoglobulin G (IgG) synthesis in the central nervous system (CNS) is vital for diagnosing inflammatory neurological conditions like multiple sclerosis.
- Current diagnostic approaches involve comparing serum and cerebrospinal fluid (CSF) IgG levels, but face challenges with qualitative vs. quantitative measurements.
- Similar difficulties in assessing CSF IgG exist, impacting the reliable diagnosis of CNS inflammatory diseases.
Purpose of the Study:
- To investigate discrepancies in cerebrospinal fluid (CSF) immunoglobulin G (IgG) analysis.
- To evaluate the effectiveness of different staining methods in detecting local IgG synthesis.
- To recommend improved diagnostic strategies for CNS inflammatory diseases.
Main Methods:
- Quantitative analysis of IgG using rate nephelometry.
- Separation of IgG via isoelectric focusing.
- Detection using silver stain or immunofixation, followed by scanning densitometry.
Main Results:
- Significant discrepancies were observed between CSF IgG detected by silver stain versus IgG stain methods.
- These findings indicate potential inaccuracies in traditional diagnostic approaches.
Conclusions:
- Qualitative separation techniques followed by densitometric estimation of enzyme-linked immunofixation are superior to simple quantitative nephelometric analysis with silver staining.
- The recommended methods offer improved detection of local IgG synthesis in the CNS.
- These findings support earlier recommendations for enhanced diagnostic accuracy in conditions like multiple sclerosis.
Background:
Detection of local synthesis of IgG within the central nervous system is important for the diagnosis of brain inflammatory diseases such as multiple sclerosis. This is typically done by comparing the amounts of IgG in serum and parallel cerebrospinal fluid (CSF). Although there have been well-described problems with qualitative versus quantitative measurements of abnormal IgG, such as in myeloma paraproteins, similar difficulties are also found with CSF IgG.
Methods:
Traditional quantitative analysis of IgG by rate nephelometry was followed by separation of the IgG using isoelectric focusing and then either silver stain or immunofixation. Finally, quantitative analysis was performed by scanning densitometry using public domain software downloaded from the National Institutes of Health.
Results:
We report here the major discrepancies that can occur with CSF IgG between the silver stain versus the IgG stain.
Conclusions:
We concur with the earlier recommendation that qualitative separation followed by densitometric estimation of enzyme-linked immunofixation is also more useful than simple quantitative nephelometric analysis followed by silver staining in the detection of local synthesis of IgG, analogous to the earlier work on paraproteins.
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