CSF proteome analysis in multiple sclerosis patients by two-dimensional electrophoresis.

BACKGROUND AND PURPOSE: In recent years, different approaches have been used to investigate changes of cerebrospinal fluid (CSF) proteome in patients affected by multiple sclerosis (MS) with the aim to identify protein markers with potential diagnostic or prognostic value. Because of the lack of standardization of current proteomic techniques, contrasting results were achieved until now in different laboratories. In this study, we compare CSF proteome of 10 relapsing-remitting MS (RR-MS) patients, 11 patients with clinically isolated syndrome (CIS), and 10 control subjects without neurological or systemic diseases. METHODS: The differential expression of CSF proteins amongst these cohorts of patients was investigated by using two-dimensional electrophoresis and mass spectrometry. RESULTS AND CONCLUSIONS: We found an overexpression of IgG free kappa light chain protein in both CIS and RR-MS patients, compared with control subjects and an increased expression of an apolipoprotein E isoform in RR-MS patients, compared with CIS and control groups. Our results confirm the presence of CSF proteome changes in MS patients. Future research should be aimed to investigate the role of these candidate CSF markers in larger cohorts of CIS and MS patients.

Production of brain-derived neurotrophic factor by mononuclear cells of patients with multiple sclerosis treated with glatiramer acetate, interferon-beta 1a, and high doses of immunoglobulins.

Sixty, relapsing remitting (RR) multiple sclerosis (MS) patients, who underwent treatment with glatiramer acetate (GA), interferon (IFN)-beta 1a, and immunoglobulins (Igs) (20 per treatment group), were assessed for levels of brain-derived neurotrophic factor (BDNF) in the supernatants of unstimulated and stimulated peripheral blood mononuclear cells (PBMCs) in the first year of treatment. Phytohemagglutinin (PHA), anti-OKT3 antibody, myelin basic protein (MPB) and GA were used as stimuli. Cytokine responses by ELISPOT and lymphoproliferative responses were also assessed. The GA-treated MS patient group showed a progressive increase in BDNF levels, from baseline to month three; thereafter, the levels remained stable and significantly greater compared with baseline and controls (ANOVA=P<0.001). IFN-beta 1a had no effect on BDNF production, whereas Igs induced a slight decrease (ANOVA=P<0.04). ELISPOT analysis revealed a significant decrease of IFN-gamma, an increase of interleukin (IL)-4 and IL-5 in GA-treated MS patients, and an increase of IL-10 in patients treated with IFN-beta 1a and GA. No significant correlation was found between BDNF secretion in the supernatants of PBMCs and cytokine response, lesional load, and measures of atrophy. Increased BDNF production related to GA treatment can have implications for understanding the mechanism of action of this immunomodulatory agent, in light of evidence suggesting its effects in promoting neuroprotective immunity in MS patients; however, a clinically measurable effect, especially in terms of an impact on actual disease progression, remains to be established.

Glial cell line-derived neurotrophic factor and somatostatin levels in cerebrospinal fluid of patients affected by chronic migraine and fibromyalgia.

The aim of the present study was to verify cerebrospinal fluid (CSF) levels of glial cell line-derived neurotrophic factor (GDNF) and somatostatin, both measured by sensitive immunoassay, in: 16 chronic migraine (CM) patients, 15 patients with an antecedent history of migraine without aura diagnosed as having probable chronic migraine (PCM) and probable analgesic-abuse headache (PAAH), 20 patients affected by primary fibromyalgia syndrome (PFMS), and 20 control subjects. Significantly lower levels of GDNF and somatostatin were found in the CSF of both CM and PCM + PAAH patients compared with controls (GDNF =P < 0.001, P < 0.002; somatostatin = P < 0.002, P < 0.0003), without significant difference between the two groups. PFMS patients, with and without analgesic abuse, also had significantly lower levels of both somatostatin and GDNF (P < 0.0002, P < 0.001), which did not differ from those of CM and PCM + PAAH patients. A significant positive correlation emerged between CSF values of GDNF and those of somatostatin in CM (r = 0.70, P < 0.02), PCM + PAAH (r = 0.78, P < 0.004), and PFMS patients (r = 0.68, P < 0.008). Based on experimental findings, it can be postulated that reduced CSF levels of GDNF and somatostatin in both CM and PCM + PAAH patients can contribute to sustained central sensitization underlying chronic head pain. The abuse of simple or combination analgesics does not seem to influence the biochemical changes investigated, which appear to be more strictly related to the chronic pain state, as demonstrated also for fibromyalgia.