Contributions
Abstract: EP1478
Type: Poster Sessions
Abstract Category: Pathology and pathogenesis of MS - Immunology
Multiple sclerosis (MS) is a chronic neuroinflammatory condition with associated demyelination and neurodegeneration. The most common type of MS is relapsing-remitting (RRMS) where new symptoms occur in isolated attacks (relapses). The relapses can consist of new physical disability, cognitive deficits, or optic neuritis. Between the attacks, the symptoms may dissipate completely; however permanent neurological deficits can often remain leading to accumulation of disability. MS generally affects those in their early 30s and 40s and therefore the lifelong burden of disease and the effects of MS on quality of life can be very devastating. In this study we will look at the peripheral immune system and in particular the contribution of innate immune cells, monocytes, to MS relapse. Monocytes are immunoresponsive cells in the blood stream and they respond to various injurious agents by becoming activated and releasing various biologically active factors. The plaques of MS in the brain, spinal cord and along the optic nerve consist of large numbers of monocytes and their counterpart cells microglia (immunocompetent cells of the CNS). There is a large cohort of data indicating that monocyte and microglial activation can contribute to worsening disease and can play an important role in acute attacks. Microglia and monocytes express a purinergic (ATP sensing) receptor on their cell membrane, called, P2X7 receptor (P2X7R). We have previously shown that P2X7R expression can cause microglial activation. In this study we will be examining the role of monocytes and P2X7R in the setting of MS relapse. Patients who are having an acute MS relapse are recruited into this study, and 50mL of blood is collected from them. The blood is used to isolate and culture their monocytes, as well as processing of serum for proteomic analysis and enzyme linked assays for various cytokines and chemokines. We have been able to show that monocytes from patients with RRMS at the time of MS relapse express P2X7R with increased P2X7R channel activity. The proinflammatory cytokine, interleukin 1β was also elevated from monocytes derived from patients with MS relapse and when exposed to GMCSF (granulocyte colony stimulating factor). Our data thus far highlights a critical role for P2X7R in MS relapse indicating that antagonism of this receptor could serve a key therapeutic strategy to combat the peripheral and central inflammation that is seen during MS flare.
Disclosure: I do not have any conflicts of interest.
I have received travel assistance by Merck.
Abstract: EP1478
Type: Poster Sessions
Abstract Category: Pathology and pathogenesis of MS - Immunology
Multiple sclerosis (MS) is a chronic neuroinflammatory condition with associated demyelination and neurodegeneration. The most common type of MS is relapsing-remitting (RRMS) where new symptoms occur in isolated attacks (relapses). The relapses can consist of new physical disability, cognitive deficits, or optic neuritis. Between the attacks, the symptoms may dissipate completely; however permanent neurological deficits can often remain leading to accumulation of disability. MS generally affects those in their early 30s and 40s and therefore the lifelong burden of disease and the effects of MS on quality of life can be very devastating. In this study we will look at the peripheral immune system and in particular the contribution of innate immune cells, monocytes, to MS relapse. Monocytes are immunoresponsive cells in the blood stream and they respond to various injurious agents by becoming activated and releasing various biologically active factors. The plaques of MS in the brain, spinal cord and along the optic nerve consist of large numbers of monocytes and their counterpart cells microglia (immunocompetent cells of the CNS). There is a large cohort of data indicating that monocyte and microglial activation can contribute to worsening disease and can play an important role in acute attacks. Microglia and monocytes express a purinergic (ATP sensing) receptor on their cell membrane, called, P2X7 receptor (P2X7R). We have previously shown that P2X7R expression can cause microglial activation. In this study we will be examining the role of monocytes and P2X7R in the setting of MS relapse. Patients who are having an acute MS relapse are recruited into this study, and 50mL of blood is collected from them. The blood is used to isolate and culture their monocytes, as well as processing of serum for proteomic analysis and enzyme linked assays for various cytokines and chemokines. We have been able to show that monocytes from patients with RRMS at the time of MS relapse express P2X7R with increased P2X7R channel activity. The proinflammatory cytokine, interleukin 1β was also elevated from monocytes derived from patients with MS relapse and when exposed to GMCSF (granulocyte colony stimulating factor). Our data thus far highlights a critical role for P2X7R in MS relapse indicating that antagonism of this receptor could serve a key therapeutic strategy to combat the peripheral and central inflammation that is seen during MS flare.
Disclosure: I do not have any conflicts of interest.
I have received travel assistance by Merck.