Vitamin D deficiency in relation with the systemic and central inflammation during multiple sclerosis.

Background: During the last decade, vitamin D (VitD) has become a topic of interest in immune regulation, especially in multiple sclerosis (MS) disease. Amongst the wide range of effects reported for this vitamin on the immune system, a regulatory role on cytokines production has been described. Our aim is to analyze the status of VitD and its correlation with the circulating inflammation and the intrathecal humoral response during MS. Methods: We analyzed samples of 318 individuals: 108 MS patients and 210 controls. Determination of 25-(OH) VitD3 level in serum was made using electrochemiluminescence method. Circulating inflammatory cytokines (IL-6, IL-8, IL-10, TNF-a, IL12p70 and IL-1b) were investigated using Cytometer Bead Array Technology. The central humoral response was characterized using CSF isofocusing test and IgG Index calculation. Results: As expected, mean value of VitD was significantly lower in MS group (26 nmol/L) than in control group (34.75 nmol/L) (p=0.002), with a severe deficiency in 67% of MS patients. Mean value of VitD was significantly lower in MS female patients. Regarding cytokines, mean value of TNFa was significantly higher in MS patients with oligoclonal bands of IgG in the CSF. IL6 was positively correlated with IgG level in serum of MS patients. Conclusions: Our results support the association of VitD deficiency with MS, especially in female patients of our region. However, the vitamin level seems to not correlate with inflammatory cytokines nor with disability. Interestingly, TNFa and IL6 levels were correlated with the intrathecal synthesis of IgG and the circulating IgG level, respectively.

Intrathecal B cell-related markers for an optimized biological investigation of multiple sclerosis patients.

In multiple sclerosis (MS) disease, the importance of the intrathecal B cell response classically revealed as IgG oligoclonal bands (OCB) in cerebrospinal fluid (CSF) was reaffirmed again in the recently revised diagnostic criteria. We aimed to optimize Laboratory investigation by testing the performance of new B cell-related molecules in CSF (Ig free light chains (FLCκ and λ) and CXCL13 (B-Cell Attracting chemokine1)) for MS diagnosis. 320 paired (CSF-serum) samples were collected from 160 patients with MS (n = 82) and non-MS diseases (n = 78). All patients benefited from IgG index determination, OCB detection, CSF CXCL13 and FLC (κ and λ) measurement in CSF and serum for metrics calculation (κ/λ ratio, FLC-related indexes, and κFLC-intrathecal fraction (IF)). CXCL13 and FLC metrics in CSF were higher in patients with MS and positive OCB. As expected, κFLC metrics-in particular, κFLC index and κFLC IF-had the highest accuracy for MS diagnosis. κ index showed the best performance (sensitivity 83% and specificity 91.7%) at a cut-off of 14.9. Most of the FLC-related parameters were positively correlated with IgG index and the level of CXCL13. In conclusion, the quantitative, standardizable, and technically simple CSF FLCκ metrics seem to be reliable for MS diagnosis, but could not replace OCB detection. CXCL13 appears to be an effective parameter reflecting the intrathecal B cell response. An optimized way for CSF testing combining the conventional and the new B cell-related parameters is proposed in this study.