BAFF Index and CXCL13 levels in the cerebrospinal fluid associate respectively with intrathecal IgG synthesis and cortical atrophy in multiple sclerosis at clinical onset

Background: 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. methods: paired cerebrospinal fluid (csf) and serum specimens from 40 clinically isolated syndrome suggestive of ms or early-onset relapsing-remitting ms patients (cis/errms) and 17 healthy controls (hc) were analyzed for the intrathecal synthesis of igg (quantitative formulae and igg oligoclonal bands,iggob),cxcl13,baff,and il-21. 3d-flair,3d-dir,and 3d-t1 mri sequences were applied to evaluate white matter (wm) and gray matter (gm) lesions and global cortical thickness (gcth). results: compared to hc,cis/errms having iggob (iggob+,26 patients) had higher intrathecal igg indexes (p<0.01),lower values of baff index (11.9±6.1 vs 17.5±5.2,p<0.01),and higher csf cxcl13 levels (27.7±33.5 vs 0.9±1.5,p<0.005). in these patients,baff index but not csf cxcl13 levels inversely correlated with the intrathecal igg synthesis (r>0.5 and p<0.05 for all correlations). csf leukocyte counts were significantly higher in iggob+ compared to iggob- (p<0.05) and hc (p<0.01),and correlated to csf cxcl13 concentrations (r 0.77,p<0.001). the gcth was significantly lower in patients with higher csf cxcl13 levels (2.41±0.1 vs 2.49±0.1mm,p<0.05),while no difference in mri parameters of wm and gm pathology was observed between iggob+ and iggob-. conclusions: the intrathecal igg synthesis inversely correlated with baff index and showed no correlation with csf cxcl13. these findings seem to indicate that intrathecally synthesized igg are produced by long-term pcs that have entered the cns from the peripheral blood,rather than produced by pcs developed in the meningeal follicle-like structures (fls). in this study,cxcl13 identifies a subgroup of ms patients characterized by higher leukocyte counts in the csf and early evidence of cortical thinning,further suggesting a role for this chemokine as a possible marker of disease severity. © 2017 the author(s).