Prognostic value of free light chains lambda and kappa in early multiple sclerosis.

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.

Evidence for an Intrathecal Immunoglobulin Synthesis by Kappa Free Light Chains in Neurological Patients with an Isolated Band in Isoelectric Focusing.

The gold standard for detecting intrathecal immunoglobulin synthesis is the determination of the oligoclonal band (OCB) in the cerebrospinal fluid (CSF) using isoelectric focusing (IEF). Controversy still exists regarding the significance of an isolated band in the CSF. A highly promising alternative method for the assessment of intrathecal inflammation is the quantification of kappa free light chains (k-FLC). Our aim was to evaluate the clinical significance of quantitative k-FLC in patients with an isolated band in the CSF. Using the Human Kappa Freelite Mx Kit on a turbidimetric Optilite®, we quantified the k-FLCs in paired CSF and serum samples in 47 patients with a single band in IEF. We classified patients into 27× inflammatory neurological disorders (IND), 2× peripheral inflammatory neurological disorders (PIND), 9× non-inflammatory neurological disorders (NIND) and 9× symptomatic controls (SC) based on their medical diagnosis. k-FLC were below the lower measurement limit of the analyser (LML) in all SC and PIND, as well as in 8 out of 9 NIND and 11 IND. Only 1 NIND and 16 IND were above the LML, and of these, only 14 IND were above the upper discrimination limit (Qlim). A neuroinflammatory nature of the diseases can be indicated in many cases by positive k-FLC in patients with an isolated band in IEF. The measurement of k-FLC can support the diagnosis of neurological diseases if they are included in the routine work-up.

Decreased Cerebrospinal Fluid Antioxidative Capacity Is Related to Disease Severity and Progression in Early Multiple Sclerosis.

Background: Oxidative stress-induced neuronal damage in multiple sclerosis (MS) results from an imbalance between toxic free radicals and counteracting antioxidants, i.e., antioxidative capacity (AOC). The relation of AOC to outcome measures in MS still remains inconclusive. We aimed to compare AOC in cerebrospinal fluid (CSF) and serum between early MS and controls and assess its correlation with clinical/radiological measures. Methods: We determined AOC (ability of CSF and serum of patients to inhibit 2,2'-azobis(2-amidinopropane) dihydrochloride-induced oxidation of dihydrorhodamine) in clinically isolated syndrome (CIS)/early relapsing-remitting MS (RRMS) (n = 55/11) and non-inflammatory neurological controls (n = 67). MS patients underwent clinical follow-up (median, 4.5; IQR, 5.2 years) and brain MRI at 3 T (baseline/follow-up n = 47/34; median time interval, 3.5; IQR, 2.1 years) to determine subclinical disease activity. Results: CSF AOC was differently regulated among CIS, RRMS and controls (p = 0.031) and lower in RRMS vs. CIS (p = 0.020). Lower CSF AOC correlated with physical disability (r = -0.365, p = 0.004) and risk for future relapses (exp(ß) = 0.929, p = 0.033). No correlations with MRI metrics were found. Conclusion: Decreased CSF AOC was associated with increased disability and clinical disease activity in MS. While our finding cannot prove causation, they should prompt further investigations into the role of AOC in the evolution of MS.