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Please use this identifier to cite or link to this item: http://hdl.handle.net/1942/26012

Title: Novel Antibody Targets in Spinal Cord Injury: Study of their Biomarker Potential and Biological Relevance
Authors: Palmers, Ilse
Advisors: Somers, Veerle
Hendrix, Sven
Issue Date: 2018
Abstract: Spinal cord injury (SCI) is a sudden and unexpected condition resulting in temporary or permanent disruption of motor, sensor and/or autonomic functions. As the patients’ quality of life is dramatically affected and current treatment strategies are unable to induce complete neurological or functional recovery, an accurate diagnosis and prognosis prediction is essential. The diagnosis of SCI is mostly straightforward and based on neurological symptoms and magnetic resonance imaging (MRI). A reliable prognosis prediction is more challenging as the current prognostic tools have various limitations and give only limited information on the severity of the lesion. Therefore, the identification of disease markers that can support the current prognostic tools is warranted. Furthermore, clinically relevant markers that are associated with the disease can give more insight into the pathological processes after SCI and can contribute to the development of novel treatment strategies. Recent studies highlight the pivotal role of B cells and antibodies in SCI-induced neuroinflammation. Animal models have shown that B cells and antibodies clearly contribute to aggravated tissue damage and impaired neurological recovery after SCI. However, the identity of SCI-induced antibody targets remains unclear. In SCI patients, elevated levels of antibodies to several central nervous system (CNS) lipids and proteins such as GM1 gangliosides and myelin-associated glycoprotein have been detected in serum. Despite these findings, there is no substantial evidence yet for a relevant role of B cells and antibodies in SCI-induced disease processes in humans. Therefore, a comprehensive analysis of patient samples is needed to establish the true prevalence, specificity and pathogenic relevance of SCI-induced antibodies in humans. The goal of this study was to determine the antibody reactivity profile after SCI using serological antigen selection (SAS) in order to identify novel disease markers for SCI patients and to discover biologically relevant antibody responses. Two of the newly identified antigenic targets, UH.SCI.2 and UH.SCI.7, correspond to parts of the proteins 26S proteasome non-ATPase regulatory subunit 4 (PSMD4) and protein S100-B (S100B), respectively. For both antigenic targets we confirmed the in vivo identity. Using our in-house optimized peptide ELISA, PSMD4 and S100B autoantibodies were further characterized within SCI patients and other study populations for their clinical relevance. Subsequently, we explored the biological relevance of PSMD4 and PSMD4 autoantibodies in SCI pathology.
URI: http://hdl.handle.net/1942/26012
Category: T1
Type: Theses and Dissertations
Appears in Collections: PhD theses
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