Validation of an alternative algorithm to oligoclonal bands. Free Light Chains in Cerebrospinal Fluid: Quantitative and Qualitative method.

BACKGROUND

Nearly 85% of patients with Multiple Sclerosis (MS) present oligoclonal bands (OB) by isoelectric focusing (IEF) in their cerebrospinal fluid (CSF). Currently, it is proposed to quantify free light chains (FLC), as a potential alternative for the analysis of intrathecal synthesis of immunoglobulins (ISI).

OBJECTIVES

To study FLC in CSF/serum by qualitative/quantitative methods, in comparison with the IEF.

METHODS

Paired CSF/serum samples from 81 patients with a medical request for OB by IEF were analyzed. The FLC index was calculated: CSF/serum FLC quotient with reference to the albumin CSF/serum concentration (κ-Index and λ-Index). To analyze the dimer-monomer patterns of FLC in CSF-serum, qualitative Western blot (WB) immunoassay was performed with anti-κ and anti-λ antisera.

RESULTS

A cut-off limit was obtained for κ-Index=20 and λ-Index=17, sensitivity 70% and 28%; and specificity 95% and 92%, respectively. The WB was positive when a higher proportion of κ-monomer (WBκ) and/or λ-dimer (WBλ) was observed in CSF versus serum. Sensitivity for WBκ and WBλ was 80% and 82% respectively, specificity of 93% for both. The combined use of κ-Index<20 and the presence of κ-monomer and/or λ-dimer by WB increased the sensitivity to 100%.

CONCLUSIONS

We propose analysis by WB when κ-Index<20, as an alternative algorithm to OB by IEF, for the investigation of ISI in CSF.