MS B-cells in vitro do weird things. CCSVI link?

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MS B-cells in vitro do weird things. CCSVI link?

Post by frodo » Tue Jun 26, 2018 12:33 am

This is an article that I am reading slowly, as I do not understand most of the things it says. But the summary is that MS B-cells do weird things. Something that was already suspected, because B-cells depletion with anti-CD20 MABs is the best thing we have at this time against MS.

It seems that the researchers have extracted B-cells from MS patients and infected them with the Epstein-Barr virus EBV. After that, it seems that they become "inmortalized", both in patients and in controls, but it happens more often in patients. They also have noticed that the B-cells can produce "tertiary lymphoid follicles". Probably that means the "ectopic tertiary follicles" that other people report that appears in the meninges and which is related to gray matter lesions.

This article links what we know about B-cells with the EBV hypothesis, and just by the way, it also speaks about the vascular endothelial growth factor (VEGF), that could explain the observations made by the people of CCSVI research.

Intrathecal B cells in MS have significantly greater lymphangiogenic potential compared to B cells derived from non-MS subjects ... 4/abstract

Although B cell depletion is an effective therapy of multiple sclerosis (MS), the pathogenic functions of B cells in MS remain incompletely understood. We asked whether cerebrospinal fluid (CSF) B cells in MS secrete different cytokines than control-subject B cells and whether cytokine secretion affects MS phenotype.

We blindly studied CSF B cells after their immortalization by Epstein-Barr Virus (EBV) in prospectively-collected MS patients and control subjects with other inflammatory-(OIND) or non-inflammatory neurological diseases (NIND) and healthy volunteers (HV).

The pilot cohort was analyzed using intracellular cytokine staining (n=101 B cell lines [BCL] derived from 80 subjects). We validated differences in cytokine production in newly-generated CSF BCL (n=207 derived from subsequent 111 prospectively-recruited subjects representing validation cohort), using ELISA enhanced by objective, flow-cytometry-based B cell counting.

After unblinding the pilot cohort, the immortalization efficiency was almost 5 times higher in MS patients compared to controls (p<0.001). MS subjects’ BCLs produced significantly more vascular endothelial growth factor (VEGF) compared to control BCLs. Progressive MS patients BCLs produced significantly more tumor necrosis factor (TNF)-α and lymphotoxin (LT)-α than BCL from relapsing-remitting MS (RRMS) patients.

In the validation cohort, we observed lower secretion of IL-10, but also IL-1b in RRMS patients, compared to HV+NIND cohort. The validation cohort validated enhanced VEGF-C production by BCL from RRMS patients and higher TNF-α and LT-α secretion by BCL from progressive MS.

No significant differences among diagnostic categories were observed in secretion of IL-6 or GM-CSF. All three cytokines with increased secretion in different stages of MS (i.e. VEGF-C, TNF-α and LT-α enhance lymphangiogenesis, suggesting that intrathecal B cells directly facilitate the formation of tertiary lymphoid follicles, thus compartmentalizing inflammation to the central nervous system.

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