Cerebrospinal fluid kappa and lambda free light chains in oligoclonal band-negative patients with suspected multiple
D Ferraro1,2, A Trovati1, R Bedin2
1Neurology Unit, Azienda Ospedaliero-Universitaria of Modena, Modena.
Insights
The kappa index, measuring cerebrospinal fluid (CSF) kappa free light chains (FLCs), aids in diagnosing multiple sclerosis (MS) in patients negative for oligoclonal bands (OCBs). This marker shows promise for identifying MS with high probability.
Area of Science:
- Neurology
- Immunology
- Biochemistry
Background:
- Cerebrospinal fluid (CSF) kappa free light chains (FLCs) may offer superior sensitivity for detecting intrathecal immunoglobulin (Ig)G synthesis compared to oligoclonal bands (OCBs).
- Multiple sclerosis (MS) diagnosis can be challenging, particularly in cases where OCBs are absent.
- The kappa and lambda index, calculated using CSF and serum FLCs and albumin levels, is explored for its diagnostic utility.
Purpose of the Study:
- To evaluate the added value of the kappa and lambda index in predicting a diagnosis of MS.
- To assess the diagnostic performance in a cohort of OCB-negative patients suspected of having MS.
Main Methods:
- A retrospective analysis was conducted on 391 OCB-negative patients with suspected/possible MS and 54 OCB-positive MS patients.
- CSF and serum kappa and lambda FLCs were quantified using Freelite and Freelite Mx assays.
- The kappa index was analyzed using both quantitative (cut-off 5.8) and qualitative (cut-off 5.9) approaches.
Main Results:
- CSF kappa FLC levels were below detection limits in 61% of patients.
- A kappa index ≥5.8 identified 25% of OCB-negative MS patients and 98% of OCB-positive MS patients.
- Using a kappa index ≥5.9, 24% of OCB-negative MS patients were identified, compared to 5.4% of OCB-negative non-MS patients (P < 0.001).
- The lambda index provided unreliable data due to low detection rates (90% below limit).
Conclusions:
- The kappa index can assist in identifying OCB-negative patients with a high likelihood of MS.
- Enhanced sensitivity of diagnostic techniques may improve the kappa index's performance.
- Further research is needed to clarify the role of the lambda index in MS diagnosis.
Background And Purpose:
Cerebrospinal fluid (CSF) kappa free light chains (FLCs) may be a more sensitive marker of intrathecal immunoglobulin (Ig)G synthesis compared with oligoclonal bands (OCBs). Our aim was to retrospectively determine the additional value of the kappa and lambda index (CSF FLC/serum FLC)/(CSF albumin/serum albumin) in predicting a multiple sclerosis (MS) diagnosis in a group of OCB-negative patients with suspected MS.
Methods:
The CSF and serum kappa and lambda FLCs were tested using the Freelite kit (serum) and Freelite Mx (CSF) assay (The Binding Site Group, Bimingham, UK) in 391 OCB-negative patients with suspected/possible MS and in 54 OCB-positive patients with MS.
Results:
The CSF kappa FLC levels were below the detection limit (0.27 mg/L) in 61% of patients. Using quantitative data, we found the best kappa index cut-off value for the prediction of MS to be 5.8. A kappa index ≥5.8 was present in 25% of OCB-negative MS (23/92) and in 98% of OCB-positive patients with MS. Using a qualitative approach and a kappa index cut-off of 5.9, based on literature data, we likewise found that 24% of OCB-negative patients with MS had a kappa index ≥5.9, compared with 5.4% of OCB-negative patients without MS (P < 0.001). No reliable data could be obtained for the lambda index; lambda FLCs were below the detection limit (0.68 mg/L) in 90% of CSF samples.
Conclusions:
The kappa index could contribute to the identification of OCB-negative patients with a high probability of an MS diagnosis. Using more sensitive techniques might even improve the diagnostic performance of the kappa index and better define the role of the lambda index.
