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Investigation of the Antibody Respon...

Ulndreaj, Antigona.

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Investigation of the Antibody Response and the Role of IgM Immunoglobulin in Experimental Cervical Spinal Cord Injury.

Record Type:	Electronic resources : Monograph/item
Title/Author:	Investigation of the Antibody Response and the Role of IgM Immunoglobulin in Experimental Cervical Spinal Cord Injury./
Author:	Ulndreaj, Antigona.
Published:	Ann Arbor : ProQuest Dissertations & Theses, : 2019,
Description:	246 p.
Notes:	Source: Dissertations Abstracts International, Volume: 81-05, Section: B.
Contained By:	Dissertations Abstracts International81-05B.
Subject:	Neurosciences. -
Online resource:	http://pqdd.sinica.edu.tw/twdaoapp/servlet/advanced?query=13896176
ISBN:	9781392648636

Investigation of the Antibody Response and the Role of IgM Immunoglobulin in Experimental Cervical Spinal Cord Injury.
Ulndreaj, Antigona.

Investigation of the Antibody Response and the Role of IgM Immunoglobulin in Experimental Cervical Spinal Cord Injury. - Ann Arbor : ProQuest Dissertations & Theses, 2019 - 246 p.

Source: Dissertations Abstracts International, Volume: 81-05, Section: B.

Thesis (Ph.D.)--University of Toronto (Canada), 2019.

This item must not be sold to any third party vendors.

Traumatic spinal cord injury (SCI) results in motor, autonomic and sensory impairment, and is a condition for which there are no established therapies that promote repair or regeneration. Antibody responses are dysregulated in traumatic SCI, leading to increased infections and autoimmunity. However, the status of antibody responses in cervical SCI (cSCI), the most common injury level seen in patients is unknown. In this thesis, I characterized the antibody responses in a clinically relevant rodent model of cSCI. There was an autoantibody response against the spinal cord in the subacute phase (2 weeks post-injury), which did not persist in the chronic phases (10 and 20 weeks post-injury) of the condition. I observed localization of IgG and IgM antibodies in the injured spinal cord, which appeared to target perilesional astrocytes and ventral horn neurons. In parallel, I found that peripheral T- and B-cell frequencies and total serum immunoglobulins were decreased 2 weeks after injury, suggesting that peripheral immune suppression and spinal cord-targeted autoreactivity co-exist in cSCI. Additionally, I found increased serum IgM immunoglobulin at 10 weeks post-injury. As IgM immunoglobulin is important in homeostasis against autoimmunity, I investigated the role of IgM immunoglobulin in IgG-mediated autoimmunity after cSCI. Mice that lacked secreted IgM were found to have impaired neurobehavioral recovery, increased lesion size and less spared white matter in their spinal cords after cCSI, as compared to wild-type controls. Moreover, IgM-deficient mice had higher complement-fixing IgG antibody deposition in the spinal cord, coupled by increased T-lymphocyte and microglia/macrophages. Taken together, these data suggest that IgM immunoglobulin serves to regulate detrimental IgG deposition during the recovery phase after SCI.In conclusion, I demonstrated that cSCI provokes an autoantibody response against the spinal cord, in conjunction with peripheral immune suppression, during the subacute phase of injury. I have also shown that IgM immunoglobulin is necessary for spontaneous recovery in cSCI, by limiting detrimental IgG deposition in the lesioned spinal cord. These novel findings advance our knowledge of the immune-mediated pathology after cSCI and warrant the further investigation of the therapeutic potential of IgM immunoglobulin during the subacute phase of SCI.

ISBN: 9781392648636Subjects--Topical Terms:

588700
Neurosciences.
Subjects--Index Terms:

Autoantibodies

Investigation of the Antibody Response and the Role of IgM Immunoglobulin in Experimental Cervical Spinal Cord Injury.
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500 $a Source: Dissertations Abstracts International, Volume: 81-05, Section: B.
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506 $a This item must not be sold to any third party vendors.
520 $a Traumatic spinal cord injury (SCI) results in motor, autonomic and sensory impairment, and is a condition for which there are no established therapies that promote repair or regeneration. Antibody responses are dysregulated in traumatic SCI, leading to increased infections and autoimmunity. However, the status of antibody responses in cervical SCI (cSCI), the most common injury level seen in patients is unknown. In this thesis, I characterized the antibody responses in a clinically relevant rodent model of cSCI. There was an autoantibody response against the spinal cord in the subacute phase (2 weeks post-injury), which did not persist in the chronic phases (10 and 20 weeks post-injury) of the condition. I observed localization of IgG and IgM antibodies in the injured spinal cord, which appeared to target perilesional astrocytes and ventral horn neurons. In parallel, I found that peripheral T- and B-cell frequencies and total serum immunoglobulins were decreased 2 weeks after injury, suggesting that peripheral immune suppression and spinal cord-targeted autoreactivity co-exist in cSCI. Additionally, I found increased serum IgM immunoglobulin at 10 weeks post-injury. As IgM immunoglobulin is important in homeostasis against autoimmunity, I investigated the role of IgM immunoglobulin in IgG-mediated autoimmunity after cSCI. Mice that lacked secreted IgM were found to have impaired neurobehavioral recovery, increased lesion size and less spared white matter in their spinal cords after cCSI, as compared to wild-type controls. Moreover, IgM-deficient mice had higher complement-fixing IgG antibody deposition in the spinal cord, coupled by increased T-lymphocyte and microglia/macrophages. Taken together, these data suggest that IgM immunoglobulin serves to regulate detrimental IgG deposition during the recovery phase after SCI.In conclusion, I demonstrated that cSCI provokes an autoantibody response against the spinal cord, in conjunction with peripheral immune suppression, during the subacute phase of injury. I have also shown that IgM immunoglobulin is necessary for spontaneous recovery in cSCI, by limiting detrimental IgG deposition in the lesioned spinal cord. These novel findings advance our knowledge of the immune-mediated pathology after cSCI and warrant the further investigation of the therapeutic potential of IgM immunoglobulin during the subacute phase of SCI.
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653 $a Spinal cord injury
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