Kappa free light chain and neurofilament light independently predict early multiple sclerosis disease activity-a cohort study.

BACKGROUND: Inter-individual courses of multiple sclerosis (MS) are extremely variable. The objective of this study was to investigate whether κ-free light chain (κ-FLC) index and serum neurofilament light (sNfL) have an additive predictive value for MS disease activity. METHODS: Patients with early MS who had cerebrospinal fluid (CSF) and serum sampling at disease onset were followed for four years. At baseline, age, sex, disease duration, number of T2-hyperintense (T2L), and contrast-enhancing T1 lesions (CEL) on MRI were determined. During follow-up, the occurrence of a second clinical attack and start of disease-modifying treatment (DMT) were registered. κ-FLC was measured by nephelometry, and κ-FLC index calculated as [CSF κ-FLC/serum κ-FLC]/albumin quotient. sNfL was determined by single-molecule array, and age- and body-mass-index adjusted Z scores were calculated. FINDINGS: A total of 86 patients at a mean age of 33 ± 10 years and with a female predominance of 67% were included; 36 (42%) patients experienced a second clinical attack during follow-up. Cox regression analysis adjusted for age, sex, T2L, CEL, disease and follow-up duration, and DMT use during follow-up revealed that both κ-FLC index as well as sNfL Z score independently predict time to second clinical attack. The chance for freedom of relapse within 12 months was 2% in patients with high levels of κ-FLC index (>100) and high sNfL Z score (>3), 30% in patients with high κ-FLC index (>100) and lower sNfL Z score (≤3), 70% in patients with lower κ-FLC index (≤100) but high sNfL Z score (>3), and 90% in patients with lower levels of κ-FLC index (≤100) and sNfL Z score (≤3). INTERPRETATION: κ-FLC index and sNfL Z score have an additive predictive value for early MS disease activity that is independent of known predictors. FUNDING: This study was funded by a grant of the charitable foundation of the Austrian Multiple Sclerosis Society.

Diagnostic value of kappa free light chain index in patients with primary progressive multiple sclerosis - a multicentre study.

Background: Kappa free light chains (κ-FLC) in the cerebrospinal fluid (CSF) are an emerging biomarker in multiple sclerosis (MS). Objective: To investigate whether κ-FLC index has similar diagnostic value in patients with primary progressive multiple sclerosis (PPMS) compared to oligoclonal bands (OCB). Methods: Patients with PPMS were recruited through 11 MS centres across 7 countries. κ-FLC were measured by immunonephelometry/-turbidimetry. OCB were determined by isoelectric focusing and immunofixation. Results: A total of 174 patients (mean age of 52±11 years, 51% males) were included. κ-FLC index using a cut-off of 6.1 was positive in 161 (93%) and OCB in 153 (88%) patients. Conclusion: κ-FLC index shows similar diagnostic sensitivity than OCB in PPMS.

Kappa-Free Light Chains in CSF Predict Early Multiple Sclerosis Disease Activity.

OBJECTIVE: To investigate whether κ-free light chain (κ-FLC) index predicts multiple sclerosis (MS) disease activity independent of demographics, clinical characteristics, and MRI findings. METHODS: Patients with early MS who had CSF and serum sampling at disease onset were followed for 4 years. At baseline, age, sex, type of symptoms, corticosteroid treatment, and number of T2 hyperintense (T2L) and contrast-enhancing T1 lesions (CELs) on MRI were determined. During follow-up, the occurrence of a second clinical attack and start of disease-modifying therapy (DMT) were registered. κ-FLCs were measured by nephelometry, and κ-FLC index calculated as [CSF κ-FLC/serum κ-FLC]/albumin quotient. RESULTS: A total of 88 patients at a mean age of 33 ± 10 years and female predominance of 68% were included; 38 (43%) patients experienced a second clinical attack during follow-up. In multivariate Cox regression analysis adjusting for age, sex, T2L, CEL, disease and follow-up duration, administration of corticosteroids at baseline and DMT during follow-up revealed that κ-FLC index predicts time to second clinical attack. Patients with κ-FLC index >100 (median value 147) at baseline had a twice as high probability for a second clinical attack within 12 months than patients with low κ-FLC index (median 28); within 24 months, the chance in patients with high κ-FLC index was 4 times as high as in patients with low κ-FLC index. The median time to second attack was 11 months in patients with high κ-FLC index whereas 36 months in those with low κ-FLC index. CONCLUSION: High κ-FLC index predicts early MS disease activity. CLASSIFICATION OF EVIDENCE: This study provides Class II evidence that in patients with early MS, high κ-FLC index is an independent risk factor for early second clinical attack.

Cerebrospinal fluid free light chains as diagnostic biomarker in neuroborreliosis.

BACKGROUND: Free light chains (FLC) have been proposed as diagnostic biomarker in patients with inflammatory central nervous system diseases. The objective of this study was to investigate the diagnostic utility of intrathecal κ- and λ-FLC synthesis in patients with neuroborreliosis. METHODS: κ- and λ-FLC were measured by nephelometry under blinded conditions in cerebrospinal fluid (CSF) and serum sample pairs of 34 patients with neuroborreliosis and compared to a cohort of 420 control patients. κ-FLC index was calculated as [CSF κ-FLC/serum κ-FLC]/[CSF albumin/serum albumin], and λ-FLC index in analogy. RESULTS: κ-FLC and λ-FLC index were significantly elevated in patients with neuroborreliosis compared to the control group. At a specificity level of 95%, κ-FLC and λ-FLC index showed a diagnostic sensitivity of 88.2% and 100%. In comparison, IgM and IgG synthesis according to Reiber formula, IgG index >0.7 and OCB status reached a sensitivity of 83.9%, 44.1%, 58.8% and 64.7%. CONCLUSION: These findings support the diagnostic value of intrathecal FLC synthesis in neuroborreliosis patients and demonstrate a valid, easy and rater-independent alternative for the detection of an intrathecal immunoglobulin production.