Dimethyl-fumarate (DMF) demonstrated efficacy and safety in relapsing–remitting multiple sclerosis (MS) in randomized clinical trials.

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.

B lymphocytes are thought to play a relevant role in multiple sclerosis (MS) pathology. The in vivo analysis of intrathecally produced B cell-related cytokines may help to clarify the mechanisms of B cell recruitment and immunoglobulin production within the central nervous system (CNS) in MS.

B-cells are thought to play a relevant role in multiple sclerosis (MS) pathology. BAFF (B cell activating factor of the TNF family) is a B-cell survival factor constitutively produced inside the CNS by astrocytes. We studied the intrathecal synthesis of BAFF in MS at clinical onset.Paired serum and cerebrospinal fluid (CSF) specimens from 40 clinically isolated syndromes (CIS) suggestive of MS or early relapse-onset MS (eRRMS) and from 18 healthy controls (HC) were analysed. Patients were classified based on the detection of oligoclonal IgG bands in the CSF (IgGOB+ and IgGOB-). BAFF was detected by highly sensitive ELISA and its ratio (CSF-BAFF/serum-BAFF, Q(BAFF)) and Index (Q(BAFF)/Q(Alb), BAFF-Index) were calculated. IgGOB+ presented lower CSF concentrations of BAFF compared to both HC and IgGOB- (p < 0.05). BAFF Index was significantly lower in IgGOB+ compared to both HC and IgGOB- (p < 0.01). A significant inverse correlation between Q(IgG) and Q(BAFF) (r: -0.4, p < 0.05) and between BAFF index and IgGIF (r: -0.4, p < 0.05) or IgG Index (r: -0.4, p = 0.05) was found in IgGOB+. The decreased CSF levels of BAFF in IgGOB+ at clinical onset suggest the absorption of this factor by intrathecally recruited B cells since the early disease phases. (C) 2016 Elsevier B.V. All rights reserved.