Abstract
BackgroundClinical and imaging follow-up coupled with cerebrospinal fluid (CSF) and possibly serum profiling could provide information on disease activity and disability evolution in multiple sclerosis patients.Case presentationWe describe the case of a relapsing-remitting MS patient whose history was characterized by failure of several therapeutic approaches and sustained disease activity. By using a highly sensitive immunoassay methodology, we examined protein expression of 70 inflammatory/cytotoxic molecules in two consecutive paired CSF and serum samples, obtained respectively in 2006 and 2013. At disease diagnosis, elevated CSF protein levels of an inflammatory pattern, including CXCL13, CXCL12, IFNγ, TNF, sTNFR1, IL8, sCD163, APRIL, BAFF, pentraxin III and MMP2 were found compared with a group of controls. At the second lumbar puncture, sustained disease activity was accompanied by considerable (more than 2 fold changes) increase expression of most of these inflammatory molecules while no significant changes in serum inflammatory markers were detected in the two consecutive serum samples.ConclusionsElevated CSF protein expression of pro-inflammatory mediators, possibly specifically associated to GM demyelination, could remain stable or increase over time in patients with active multiple sclerosis. We underline the role of fluid analysis in understanding the pathophysiology of the disease and providing information on possible markers of disease activity and evolution.
Highlights
Clinical and imaging follow-up coupled with cerebrospinal fluid (CSF) and possibly serum profiling could provide information on disease activity and disability evolution in multiple sclerosis patients.Case presentation: We describe the case of a relapsing-remitting MS patient whose history was characterized by failure of several therapeutic approaches and sustained disease activity
We have recently shown that elevated and specific intrathecal pro-inflammatory pattern, including increased CSF levels of C-X-C motif chemokine 13 (CXCL13), TNF, IFNγ, C-X-C motif chemokine 12 (CXCL12), IL6, IL8 and IL10, B cell activating factor (BAFF), A proliferation-inducing ligand (APRIL), LIGHT, TWEAK, sTNFR1, sCD163, MMP2 and pentraxin III, characterizes a subgroup of MS patients with higher levels of grey matter (GM) damage at the time of diagnosis [4]
By using t test and the non-parametric Mann-Whitney test to detect potential significant differences (p-value < 0.05) in protein levels in the two CSF samples collected at t0 and t1, we found that at time of diagnosis 42 inflammatory molecules overexpressed in CSF of our patient (Fig. 2) respect to a control group of 26 patients including 12 with non-inflammatory neurological diseases and 14 with other inflammatory neurological diseases previous examined in detail [4]
Summary
Elevated CSF protein expression of pro-inflammatory mediators, possibly associated to GM demyelination, could remain stable or increase over time in patients with active multiple sclerosis. We underline the role of fluid analysis in understanding the pathophysiology of the disease and providing information on possible markers of disease activity and evolution
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