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Abstract Details

IgG Depletion Ameliorates Pathogenic Effects of Primary Progressive MS CSF
Multiple Sclerosis
P3 - Poster Session 3 (12:00 PM-1:00 PM)
9-018

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

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.

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.

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. 

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.

 
Authors/Disclosures
Joseph M. Beaty (Tisch MS Research Center)
PRESENTER 		Mr. Beaty has nothing to disclose.
Taylor Shue (Tisch MS Center of New York) Miss Shue has nothing to disclose.
Anna Roselle (Tisch MS Research Center) No disclosure on file
Jamie Wong, PhD (Tisch Multiple Sclerosis Research Center of New York) Dr. Wong has nothing to disclose.
Saud Sadiq, BS, FAAN (Tisch Multiple Sclerosis Research Center of New York) Ms. Brewi has nothing to disclose.