Intrathecal K free light chain synthesis in multiple sclerosis at clinical onset associates with local IgG production and improves the diagnostic value of cerebrospinal fluid examination

Background. The pathological significance and the diagnostic usefulness of intrathecal lc and X free light chain (FLC) synthesis in Multiple Sclerosis (MS) are debated. Methods. Paired cerebrospinal fluid (CSF) and serum specimens from 70 relapsing remitting MS (RAMS), 40 with and 30 without CSF restricted IgG Oligoclonal Band (IgGOB), and 37 from healthy controls (HC) were analyzed. IgG, IgM, kappa FLC and lambda FLC concentrations and indexes were evaluated. All RAMS performed MRI to estimate white and grey matter (WM) pathology. Results. In HC, no intrathecal kappa or lambda FLC synthesis was found, and kappa FLC and lambda FLC Indexes were reciprocally correlated (r = 0.67, p < 0.001). In RAMS, intrathecal kappa FLC or lambda FLC synthesis was demonstrated in respectively 66% and 43% of the cases, the Q(kappa/lambda) ratio was significantly higher compared to HC (17.0 +/- 31.3 vs 0.79 +/- 0.20, p < 0.001) and the correlation between kappa FLC Index and lambda FLC Index was weak (r:0.38, p < 0.05). Intrathecal IgG synthesis was associated with kappa FLC Index (IgG Index: r2 = 0.53, ji = 0.73, p < 0.001; IgG(Loc) : r(2) = 0.37, beta = 0.61, p < 0.001; IgG(IF):r(2) = 0.69, beta = 0.83, p < 0.001), but not with lambda FLC Index, while intrathecal IgM synthesis correlated with XFLC Index (IgM Index: r = 0.41, p < 0.001; IgM(Loc): r = 0.34, p < 0.005; r = 0.45, p < 0.001), but not with kappa FLC Index. 26% of RAMS patients without CSF-restricted IgGOB had increased kappa FLCLoc. Finally, no associations were observed between any CSF and MRI parameters. Conclusions. The demonstration of intrathecal kappa FLC synthesis may further improve the diagnostic usefulness of CSF examination in RAMS. The marked in- creased in Q(kappa/lambda) further suggests a deregulated B-cell activation in MS pathology.