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The kappa index (K-Index), calculated by dividing the cerebrospinal fluid (CSF)/serum kappa free light chain (KFLC) ratio by the CSF/serum albumin ratio, is gaining increasing interest as a marker of intrathecal immunoglobulin synthesis. However, data on inter-laboratory agreement of these measures is lacking. The aim was to assess the concordance of CSF and serum KFLC measurements, and of K-index values, across different laboratories. KFLC and albumin of 15 paired CSF and serum samples were analyzed by eight participating laboratories. Four centers used Binding Site instruments and assays (B), three used Siemens instruments and assays (S), and one center used a Siemens instrument with a Binding Site assay (mixed). Absolute individual agreement was calculated using a two-way mixed effects intraclass correlation coefficient (ICC). Cohen's kappa coefficient (k) was used to measure agreement on positive (≥5.8) K-index values. There was an excellent agreement in CSF KFLC measurements across all laboratories (ICC (95% confidence interval): 0.93 (0.87–0.97)) and of serum KFLC across B and S laboratories (ICC: 0.91 (0.73–0.97)), while ICC decreased (to 0.81 (0.53–0.93)) when including the mixed laboratory in the analysis. Concordance for a positive K-Index was substantial across all laboratories (k = 0.77) and within S laboratories (k = 0.71), and very good (k = 0.89) within B laboratories, meaning that patients rarely get discordant results on K-index positivity notwithstanding the testing in different laboratories and the use of different platforms/assays. [ABSTRACT FROM AUTHOR]

• κ-index correlates negatively with verbal memory in MS. • Brain MRI-visible lesions do not mediate this link. • B cell activation may worsen cognitive function in MS. Cognitive impairment (CI) is a common and disabling feature of people with multiple sclerosis (pwMS), but its underlying mechanisms are heterogenous and not fully understood. A role of infiltrating immune cells in the meninges and brain parenchyma has been hypothesized. This study aimed to explore the hypothesis that intrathecal B cells might influence cognitive performance in pwMS. A retrospective study was performed on 39 newly diagnosed pwMS who underwent cerebrospinal fluid (CSF) analysis. Kappa (κ)-index was measured as a biomarker of intrathecal B cell activation. Cognitive performance was assessed using the Brief Repeatable Battery of Neuropsychological Tests (BRBN). Brain T2 lesions number (T2LN) and volume (T2LV) together with brain, cortical grey matter, thalamic and hippocampal volumes were calculated to account for MRI-visible damage. κ-index was higher in pwMS with verbal memory impairment (median 99.6, range 58.5–195.2 vs. median 37.2, range 2.3–396.9, p < 0.001), and it was negatively associated with BRBN tests exploring verbal memory and information processing speed. In multivariate models, higher κ-index was confirmed to be independently associated with worse scores of BRBN tests exploring verbal memory and with a higher probability of verbal memory impairment. Intrathecal B cells might drive memory impairment in pwMS independently of brain damage visible on MRI scans. [ABSTRACT FROM AUTHOR]

Cerebrospinal fluid (CSF) free light chains (FLC) may be an alternative biomarker to oligoclonal bands (OCB) in multiple sclerosis (MS). Herein, we compared the diagnostic accuracy of CSF OCB and FLC and we tested the prognostic value of FLC in a cohort of 64 MS patients and 106 controls. A κ-index >7.83 was more sensitive but less specific than OCB in discriminating MS patients from controls. Additionally, a κ-index >10.61 performed better than OCB in the discrimination between MS and controls with inflammatory neurological diseases (p <.001). In clinically isolated syndrome (CIS) patients, a κ-index >10.61 significantly predicted time to conversion to MS (p =.020). κ-index might be a valid alternative to OCB as a diagnostic biomarker for MS and might also be a prognostic marker in CIS. Unlabelled Image • κ-index is more sensitive and less specific than OCB for MS diagnosis. • κ-index performs better than OCB in discriminating MS from other inflammatory neurological diseases. • κ-index correlates with different disease characteristics in MS. • κ-index predicts disease activity in early MS patients. [ABSTRACT FROM AUTHOR]