Intrathecal kappa free light chains as markers for multiple sclerosis
D Vecchio1,2, G Bellomo3, R Serino4
1Department of Translational Medicine, Neurology Unit, University of Piemonte Orientale, Corso Mazzini 18, 28100, Novara, Italy. domizia.vecchio@gmail.com.
Insights
The cerebrospinal fluid kappa free light chain (KFLC) index accurately diagnoses multiple sclerosis (MS) and predicts disease progression in early syndromes. A "kappa-oriented" response is characteristic of MS.
Area of Science:
- Neurology
- Immunology
- Biochemistry
Background:
- Intrathecal IgG synthesis is crucial for diagnosing multiple sclerosis (MS).
- The cerebrospinal fluid (CSF) kappa free light chain (KFLC) index is a potential marker for this synthesis.
- Different interpretation methods for KFLC require comparison for optimal diagnostic and prognostic use.
Purpose of the Study:
- To compare the diagnostic efficiency of KFLC using various interpretation approaches in MS.
- To assess the prognostic value of KFLC in radiologically and clinically isolated syndromes (RIS-CIS).
Main Methods:
- Analyzed CSF and serum samples from 133 MS patients and 240 with other neurological diseases.
- Measured albumin, lambda free light chain (LFLC), and KFLC using nephelometry.
- Calculated KFLC index, LFLC index, IgG index, and CSF ratios (KFLC/LFLC, KFLC/IgG, LFLC/IgG).
Main Results:
- KFLC levels were significantly higher in MS patients compared to controls.
- KFLC index and CSF KFLC/IgG ratio demonstrated high sensitivity and moderate specificity for MS diagnosis.
- Elevated KFLC index and CSF KFLC/IgG were observed in RIS-CIS patients who later converted to MS.
Conclusions:
- KFLC markers, particularly the KFLC index and CSF KFLC/IgG ratio, are accurate in diagnosing MS.
- These KFLC markers possess prognostic value in individuals with early MS syndromes (RIS-CIS).
- A "kappa-oriented" response is a hallmark of MS and impacts prognosis in early disease stages.
Abstract:
Cerebrospinal fluid (CSF) kappa free light chain (KFLC) index has been described as a reliable marker of intrathecal IgG synthesis to diagnose multiple sclerosis (MS). Our aims were: (1) to compare the efficiency of KFLC through different interpretation approaches in diagnosing MS. (2) to evaluate the prognostic value of KFLC in radiologically and clinically isolated syndromes (RIS-CIS). We enrolled 133 MS patients and 240 with other neurological diseases (93 inflammatory including 18 RIS-CIS, 147 non-inflammatory). Albumin, lambda free light chain (LFLC) and KFLC were measured in the CSF and serum by nephelometry. We included two groups of markers: (a) corrected for blood-CSF barrier permeability: immunoglobulin G (IgG), KFLC and LFLC indexes. (b) CSF ratios (not including albumin and serum-correction): CSF KFLC/LFLC, CSF KFLC/IgG, CSF LFLC/IgG. KFLC were significantly higher in MS patients compared to those with other diseases (both inflammatory or not). KFLC index and CSF KFLC/IgG ratio showed high sensitivity (93% and 86.5%) and moderate specificity (85% and 88%) in diagnosing MS. RIS-CIS patients who converted to MS showed greater KFLC index and CSF KFLC/IgG. Despite OB are confirmed to be the gold-standard to detect intrathecal IgG synthesis, the KFLC confirmed their accuracy in MS diagnosis. A "kappa-oriented" response characterizes MS and has a prognostic impact in the RIS-CIS population.
