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CSF free light chain identification of demyelinating disease: comparison with oligoclonal banding and other CSF
Kari M Gurtner1, Eslam Shosha2, Sandra C Bryant3
1Department of Laboratory Medicine and Pathology, Mayo Clinic, Rochester, MN, USA.
Insights
Cerebrospinal fluid free light chains (cFLC) offer a simpler, more sensitive alternative to oligoclonal bands (OCBs) for diagnosing multiple sclerosis. This method reduces costs and complexity while maintaining diagnostic accuracy.
Area of Science:
- Neurology
- Clinical Chemistry
- Immunology
Background:
- Cerebrospinal fluid (CSF) immunoglobulin gamma (IgG) index and oligoclonal bands (OCBs) are standard for multiple sclerosis (MS) diagnosis.
- Measurement of CSF free light chains (FLC) presents a potential alternative to labor-intensive isoelectric focusing (IEF) for OCBs.
Purpose of the Study:
- To evaluate CSF kappa free light chains (cKFLC) as a diagnostic marker for demyelinating diseases.
- To compare the performance of cKFLC with traditional OCB testing.
Main Methods:
- Analyzed 325 paired CSF and serum specimens using cKFLC, CSF lambda FLC (cLFLC), albumin, and IgG measurements.
- Calculated various indices including kappa-index, kappa intrathecal fraction, and IgG-index.
- Assessed cKFLC performance alone and in comparison to OCBs.
Main Results:
- cKFLC alone demonstrated over 90% agreement with OCBs, outperforming other calculated markers.
- In demyelinating disease cases, cKFLC showed 86% sensitivity and 77% specificity.
- cKFLC measurement reduced the number of required analytes and complex calculations.
Conclusions:
- cKFLC offers comparable performance to OCBs with enhanced sensitivity for demyelinating diseases.
- Replacing OCBs with cKFLC simplifies the diagnostic process, reducing costs and maintaining accuracy for MS diagnosis.
Background:
Cerebrospinal fluid (CSF) used in immunoglobulin gamma (IgG) index testing and oligoclonal bands (OCBs) are common laboratory tests used in the diagnosis of multiple sclerosis. The measurement of CSF free light chains (FLC) could pose as an alternative to the labor-intensive isoelectric-focusing (IEF) gels used for OCBs.
Methods:
A total of 325 residual paired CSF and serum specimens were obtained after physician-ordered OCB IEF testing. CSF kappa (cKFLC) and lambda FLC (cLFLC), albumin and total IgG were measured. Calculations were performed based on combinations of analytes: CSF sum of kappa and lambda ([cKFLC+cLFLC]), kappa-index (K-index) ([cKFLC/sKFLC]/[CSF albumin/serum albumin]), kappa intrathecal fraction (KFLCIF) {([cKFLC/sKFLC]-[0.9358×CSF albumin/serum albumin]^[0.6687×sKFLC]/cKFLC)} and IgG-index ([CSF IgG/CSF albumin]/[serum IgG/serum albumin]).
Results:
Patients were categorized as: demyelination (n=67), autoimmunity (n=53), non-inflammatory (n=50), inflammation (n=38), degeneration (n=28), peripheral neuropathy (n=24), infection (n=13), cancer (n=11), neuromyelitis optica (n=10) and others (n=31). cKFLC measurement used alone at a cutoff of 0.0611 mg/dL showed >90% agreement to OCBs, similar or better performance than all other calculations, reducing the number of analytes and variables. When cases of demyelinating disease were reviewed, cKFLC measurements showed 86% clinical sensitivity/77% specificity.
Conclusions:
cKFLC alone demonstrates comparable performance to OCBs along with increased sensitivity for demyelinating diseases. Replacing OCB with cKFLC would alleviate the need for serum and CSF IgG and albumin and calculated conversions. cKFLC can overcome challenges associated with performance, interpretation, and cost of traditional OCBs, reducing costs and maintaining sensitivity and specificity supporting MS diagnosis.
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