The Next Generation of Biomarker Research in Spinal Cord Injury

Abstract

In traumatic spinal cord injury (SCI) patients, the assessment of the exact degree of lesion severity and neurological prognosis has proven to be extremely challenging. The current tools for predicting functional outcome in SCI patients such as clinical examination and magnetic resonance imaging are often inaccessible to unstable or polytraumatized patients, lack sensitivity, and are unreliable in the acute phase of the injury. Multiple candidate protein biomarkers known to be linked to the pathology have been studied for their potential to predict neurological outcome over time. This hypothesis-driven approach, however, has yielded only minimal success, and the reported individual markers lack sensitivity and correlation with specific outcome measures, which highlights the need for an unbiased high-throughput screening approach to identify novel candidate biomarkers. Antibodies were suggested to represent better biomarkers as their counterpart antigens, as they are highly specific and abundantly present in blood due to their inherent amplification and long half-life. Moreover, antibodies are easily accessible and are amenable to high-throughput screening. We therefore suggest an unbiased, high-throughput, and powerful antibody profiling procedure, named Serological antigen selection, based on complementary DNA (cDNA) phage display to combine the multiple benefits of stable and frequent antibodies and those of an unbiased method. The application of such an innovative and unbiased approach can complement the more traditional approaches to aid in the discovery of novel SCI-associated biomarkers.

Circulating PAMM, a novel antioxidant and anti-inflammatory protein, is elevated in acute SCI

“…Mediators of cellular and subcellular oxidative stress have received considerable attention as potential novel neuroprotective targets in acute SCI, including the involved genes, proteins and factors [2,4,8,12]. PAMM is a promising candidate biomarker for SCI because of its dual independent anti-inflammatory and anti-oxidant properties, and because SCI is characterized by both oxidative stress and inflammatory reaction [13][14][15].…”

“…SCI results in varying degrees of functional impairment based on the extent and location of trauma to the cord with high cost to both individual and society. The assessment of both injury severity and long-term neurological prognosis remain challenging after SCI [2]. While injury severity is routinely determined by neurological exam, there are instances where complete neurological testing cannot be performed (coma, intubated or nonverbal patient, presence of cast or other physical barrier).…”

cDNA phage display for the discovery of theranostic autoantibodies in rheumatoid arthritis

“…This display method has been successfully used for the isolation of serine protease inhibitors from a hookworm cDNA library [115], and a series of reports from our research group describe the construction and use of patient-and tissue-specific pVI cDNA libraries expressing colorectal cancer tumor antigens [116] and autoantigens of the autoimmune diseases RA [107], MS [22,117] and clinically isolated syndrome [118]. Recently, our research group has also reported on the construction of a novel human spinal cord cDNA phage display library [119].…”

Bioinformatics analysis of the molecular mechanisms underlying traumatic spinal cord injury

“…Pathophysiologically, the initial mechanical injury damages neurons and initiates a complex secondary injury cascade, leading to progressive cell death, ischemia and inflammation (6). It has been demonstrated that the transcriptome may reflect the pathophysiological state of the cell (7). In a number of recent bioinformatics studies, transcriptome analysis at different time points post-SCI was performed and various molecular events were characterized (8)(9)(10)(11)(12).…”

“…In a number of recent bioinformatics studies, transcriptome analysis at different time points post-SCI was performed and various molecular events were characterized (8)(9)(10)(11)(12). The immune response, inflammatory-associated functions, vasculature development and neurological functions were demonstrated to serve roles in the development of SCI (6)(7)(8)(9)(10)(11)(12). However, certain molecular alterations that occur in a temporal and spatial manner remain to be elucidated, particularly those that occur during the secondary injury process.…”