Kappa free light chains is a valid tool in the diagnostics of MS: A large multicenter study.

OBJECTIVE: To validate kappa free light chain (KFLC) and lambda free light chain (LFLC) indices as a diagnostic biomarker in multiple sclerosis (MS). METHODS: We performed a multicenter study including 745 patients from 18 centers (219 controls and 526 clinically isolated syndrome (CIS)/MS patients) with a known oligoclonal IgG band (OCB) status. KFLC and LFLC were measured in paired cerebrospinal fluid (CSF) and serum samples. Gaussian mixture modeling was used to define a cut-off for KFLC and LFLC indexes. RESULTS: The cut-off for the KFLC index was 6.6 (95% confidence interval (CI) = 5.2-138.1). The cut-off for the LFLC index was 6.9 (95% CI = 4.5-22.2). For CIS/MS patients, sensitivity of the KFLC index (0.88; 95% CI = 0.85-0.90) was higher than OCB (0.82; 95%CI = 0.79-0.85; p < 0.001), but specificity (0.83; 95% CI = 0.78-0.88) was lower (OCB = 0.92; 95% CI = 0.89-0.96; p < 0.001). Both sensitivity and specificity for the LFLC index were lower than OCB. CONCLUSION: Compared with OCB, the KFLC index is more sensitive but less specific for diagnosing CIS/MS. Lacking an elevated KFLC index is more powerful for excluding MS compared with OCB but the latter is more important for ruling in a diagnosis of CIS/MS.

Serum netrin-1 in relation to gadolinium-enhanced magnetic resonance imaging in early multiple sclerosis.

BACKGROUND: Netrin-1, a secreted laminin-related protein, is known to regulate not only axonal guidance and neuronal cell migration, but also blood-brain barrier integrity and inflammation. Two preliminary studies reported altered serum netrin-1 levels in multiple sclerosis; however, associations with longitudinal clinical and magnetic resonance imaging activity have not been investigated. OBJECTIVES: We aimed to assess serum netrin-1 in multiple sclerosis and controls with respect to disease activity and its temporal dynamics. METHODS: Serum netrin-1 was assessed by enzyme-linked immunosorbent assay in 79 patients with clinically isolated syndrome or multiple sclerosis, and 30 non-inflammatory neurological disease controls. In patients, serum samples were collected immediately prior to gadolinium-enhanced 3 T magnetic resonance imaging at two time points (initial contrast-enhancing gadolinium+ n = 47, non-enhancing gadolinium- n = 32; reference gadolinium- n = 70; median time-lag 1.4, interquartile range 1.0-2.3 years). RESULTS: Serum netrin-1 levels were similar in clinically isolated syndrome, multiple sclerosis and controls, and gadolinium+ and gadolinium- patients. Among gadolinium+ patients, serum netrin-1 was decreased in clinically active (n = 8) vs non-active patients (n = 39; p = 0.041). Serum netrin-1 showed no temporal dynamics in multiple sclerosis and was unrelated to clinical data. CONCLUSIONS: Serum netrin-1 levels show no multiple sclerosis specific changes and are not sensitive for detection of subclinical disease activity. Netrin-1 changes during relapses may deserve further examination.