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Prognostic value of free light chains lambda and kappa in early multiple sclerosis
Margarete M Voortman1, Tatjana Stojakovic2, Lukas Pirpamer1
1Department of Neurology, Medical University of Graz, Graz, Austria.
Background:
Cerebrospinal fluid (CSF) immunoglobulin free light chains (FLC) have been suggested as quantitative alternative to oligoclonal bands (OCB) in the diagnosis of multiple sclerosis (MS). However, little is known on their role in predicting clinical and paraclinical disease progression, particularly in early stages.
Objective:
To assess the prognostic value of FLC in OCB-positive patients with clinically isolated syndrome (CIS) suggestive of MS and early MS.
Methods:
We determined FLC kappa (KFLC) and lambda (LFLC) in CSF and serum by nephelometry in 61 patients (CIS ( n = 48), relapsing-remitting multiple sclerosis ( n = 13)) and 60 non-inflammatory neurological controls. Median clinical follow-up time in CIS was 4.8 years (interquartile range (IQR), 1.5-6.5 years). Patients underwent 3T magnetic resonance imaging (MRI) at baseline and follow-up (median time interval, 2.2 years; IQR, 1.0-3.7 years) to determine T2 lesion load (T2LL) and percent brain volume change (PBVC).
Results:
CSF FLC were significantly increased in CIS/MS compared to controls (all p < 0.001). A lower KFLC/LFLC CSF ratio was associated with CIS-clinically definite multiple sclerosis (CDMS) conversion (hazard ratio (HR) = 2.89; 95% confidence interval (CI) = 1.17-7.14; p < 0.05). No correlations were found for FLC variables with T2LL or PBVC.
Conclusion:
Our study confirms increased intrathecal synthesis of FLC in CIS/MS which supports their diagnostic contribution. The KFLC/LFLC CSF ratio appears to have a prognostic value in CIS beyond OCB.
Insights
Cerebrospinal fluid free light chains (FLC) show prognostic value in predicting multiple sclerosis (MS) conversion from clinically isolated syndrome (CIS). A lower CSF kappa FLC/lambda FLC ratio indicates higher risk, offering insights beyond oligoclonal bands (OCB).
Area of Science:
- Neurology
- Immunology
- Biomarker Research
Background:
- Cerebrospinal fluid (CSF) immunoglobulin free light chains (FLC) are explored as a quantitative alternative to oligoclonal bands (OCB) for multiple sclerosis (MS) diagnosis.
- Limited data exists on the prognostic role of FLC in predicting disease progression, especially in early MS stages.
Purpose of the Study:
- To evaluate the prognostic significance of FLC in patients with OCB-positive clinically isolated syndrome (CIS) and early MS.
- To assess the association of FLC with clinical and MRI-based markers of disease progression.
Main Methods:
- CSF and serum KFLC and LFLC levels were measured using nephelometry in 61 CIS/MS patients and 60 controls.
- Clinical follow-up and 3T MRI (T2 lesion load, percent brain volume change) were conducted over a median of 4.8 and 2.2 years, respectively.
Main Results:
- CSF FLC levels were significantly elevated in CIS/MS patients compared to controls (p < 0.001).
- A lower CSF KFLC/LFLC ratio was associated with conversion from CIS to clinically definite MS (CDMS) (HR=2.89, p < 0.05).
- No significant correlations were observed between FLC variables and MRI measures (T2LL, PBVC).
Conclusions:
- Intrathecal synthesis of FLC is confirmed in CIS/MS, supporting their diagnostic utility.
- The CSF KFLC/LFLC ratio demonstrates prognostic value in CIS, potentially exceeding that of OCB for predicting MS conversion.
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