Cerebrospinal fluid kappa free light chains for the diagnosis of multiple sclerosis: A consensus statement
Harald Hegen1, Georgina Arrambide2, Sharmilee Gnanapavan3
1Department of Neurology, Medical University of Innsbruck, Innsbruck, Austria.
Insights
Cerebrospinal fluid analysis is crucial for diagnosing multiple sclerosis (MS). Intrathecal kappa-free light chain (κ-FLC) synthesis is a highly accurate biomarker for MS, offering advantages over traditional oligoclonal bands.
Area of Science:
- Neurology
- Immunology
- Clinical Diagnostics
Background:
- Cerebrospinal fluid (CSF) analysis is vital for diagnosing multiple sclerosis (MS).
- Intrathecal immunoglobulin G (IgG) synthesis, detected by CSF-restricted oligoclonal bands (OCBs), confirms MS inflammation.
- OCBs are the current gold standard for assessing intrathecal IgG synthesis.
Purpose of the Study:
- To evaluate kappa-free light chains (κ-FLCs) as a novel biomarker for intrathecal inflammation in MS.
- To compare the diagnostic accuracy of κ-FLCs with OCBs in MS diagnosis.
- To provide recommendations for standard CSF evaluation in suspected MS cases.
Main Methods:
- Analysis of cerebrospinal fluid (CSF) for intrathecal immunoglobulin synthesis.
- Detection of CSF-restricted oligoclonal bands (OCBs).
- Measurement of κ-free light chains (κ-FLCs) in CSF.
Main Results:
- Intrathecal κ-FLC synthesis demonstrates high diagnostic accuracy (approx. 90% sensitivity and specificity) in MS, comparable to OCBs.
- κ-FLC detection offers advantages: speed, ease, cost-effectiveness, reliability, and quantitative results.
- κ-FLCs may enhance the prediction of MS disease activity.
Conclusions:
- Intrathecal κ-FLC synthesis is a valuable and accurate biomarker for diagnosing MS.
- κ-FLCs present practical advantages over OCBs for routine CSF diagnostics.
- An expert panel recommends including κ-FLC synthesis in future MS diagnostic criteria.
Abstract:
Cerebrospinal fluid (CSF) analysis is of utmost importance for diagnosis and differential diagnosis of patients with suspected multiple sclerosis (MS). Evidence of intrathecal immunoglobulin G (IgG) synthesis proves the inflammatory nature of the disease, increases diagnostic certainty and substitutes for dissemination in time according to current diagnostic criteria. The gold standard to determine intrathecal IgG synthesis is the detection of CSF-restricted oligoclonal bands (OCBs). However, advances in laboratory methods brought up κ-free light chains (FLCs) as a new biomarker, which are produced in excess over intact immunoglobulins and accumulate in CSF in the case of central nervous system-derived inflammation. Overwhelming evidence showed a high diagnostic accuracy of intrathecal κ-FLC synthesis in MS with sensitivity and specificity of approximately 90% similar to OCB. κ-FLCs have advantages as its detection is fast, easy, cost-effective, reliable, rater-independent and returning quantitative results which might also improve the value of predicting MS disease activity. An international panel of experts in MS and CSF diagnostics developed a consensus of all participants. Six recommendations are given for establishing standard CSF evaluation in patients suspected of having MS. The panel recommended to include intrathecal κ-FLC synthesis in the next revision of MS diagnostic criteria as an additional tool to measure intrathecal immunoglobulin synthesis.
