AAN2020 News. B cells in the Brain are Bad News

This week we shouldn’t be stuck in-doors, we should have been playing whilst the Bosses were off on a jolly to the land of the As….Yep Can-an-ana-da to be with the Great and the Good at the Amercian Academy of Neurology. However, they are stuck breathing Covid-juice

We can have a trawl through the adstracts but clearly on new agent coming towards the fray are Bruton Tyrosine Kinase blockers. These were used because they are B cell inhibitory agents, however they are also macrophage inhibitors.

We need to scrub the brain clean of B cells and here is one reason why that needs to be done. Here they take the spinal cord fluid from people with primary progressive MS and they inject this into the head of a beastie and things go terrible wrong for the beasy. They then remove the antibody from the brain fluid and the problems stops, so there you have it direct evidence that there is some from of autoimmunity going on in MS. This comes as no surprise to me as has been reported before and indeed we have done it ourselvess. If fact we purified the antibody from the cerebrospinal fluid and injected the antibody. We have done this with people from MS and also people with other autoimmune CNS conditions and you get different symptoms in the beasties. In this study they get damage to the myelin, is this too good to be true as people have looked and dont’ find much evidence to support for this

1-018 – IgG Depletion Ameliorates Pathogenic Effects of Primary Progressive MS CSF. Joseph Michael Beaty

− Background
MS is characterized by inflammatory demyelination, astrogliosis and axonal loss in the CNS. Approximately 15% of MS patients are diagnosed with PPMS, which is characterized by unremitting disease progression from disease onset. We have previously reported that intrathecal delivery of PPMS CSF induces motor deficits and spinal cord pathology in mice. Here, we investigated whether depletion of IgGs from PPMS CSF prior to intrathecal administration would improve functional outcome and spinal cord pathology in mice.

Objective
To assess whether the pathogenic effects of primary progressive multiple sclerosis (PPMS) cerebrospinal fluid (CSF) are antibody-mediated.

Design Methods
CSF samples obtained from PPMS patients were incubated with DynabeadsTM Protein A for 1 hour at 4oC and Coomassie staining was performed to verify IgG reduction. PPMS CSF and IgG-depleted PPMS CSF was administered to mice intrathecally. Mice underwent laminectomies at cervical levels 4 and 5, then 3µl CSF was injected under the dura mater into the subarachnoid space. Control mice were injected with saline or CSF from healthy individuals. At 1 day post injection (DPI), functional deficits were assessed by evaluating forelimb grip strength, reaching accuracy and tail rigidity. Mice were then immediately perfused and spinal cords were processed for histological analyses.

Results
At 1DPI, PPMS CSF-injected mice exhibited significantly higher motor deficit scores and weaker grip strength compared to IgG-depleted PPMS CSF-injected mice and control mice. Demyelination, reactive astrogliosis and axonal damage were observed in the cervical spinal cords of PPMS CSF-injected mice, as demonstrated by luxol fast blue, GFAP and SMI-32 staining, respectively. However, these pathological changes were not observed in spinal cords of IgG-depleted PPMS CSF-injected mice or controls.

Conclusions
Intrathecal administration of IgG-depleted PPMS CSF does not result in motor deficits or pathology, suggesting that the pathogenic effects induced by PPMS CSF are antibody-mediated.