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The Next Generation of Biomarker Research in Spinal Cord Injury

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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.

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Abbreviations

APO:

Apolipoprotein

AIS:

ASIA impairment scale

ASIA:

American spinal injury association

AZGP1:

Zinc-alpha-2-glycoprotein

CAR:

Carbonic anhydrase

CNS:

Central nervous system

CSF:

Cerebrospinal fluid

CXCL:

C-X-C motif chemokine ligand

GFAP:

Glial fibrilar acidic protein

GTF3C5:

General transcription factor 3C polypeptide 5

Hp:

Haptoglobin

hSC:

Human spinal cord

IGHG:

Ig gamma chain C region

IL:

Interleukin

LTC4:

Leukotriene C4

MBP:

Myelin basic protein

MCP-1:

Monocyte chemoattractant protein

MMP:

Matrix metalloproteinase

MRI:

Magnetic resonance imaging

NF-L:

Neurofilament light

NSE:

Neuron-specific enolase

pNF-H:

Phosphoneurofilament heavy

PRDX2:

Peroxiredoxin-2

S100B:

S100 protein B

SAS:

Serological antigen selection

SBDP:

α-II spectrin breakdown product

SC:

Spinal cord

SCI:

Spinal cord injury

SDF-1:

Stomal-derived factor-1

TBI:

Traumatic brain injury

TNF:

Tumor necrosis factor

UCH-L1:

Ubiquitin carboxy-terminal hydrolase L1

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Acknowledgments

This study is supported by Research Foundation Flanders (FWO Vlaanderen), Hasselt University, and the Transnationale Universiteit Limburg. I. Palmers is supported by a doctoral fellowship of the Agency for Innovation by Science and Technology (IWT).

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Correspondence to Veerle Somers.

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The authors declare that they have no conflict of interest.

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Elke Ydens and Ilse Palmers contributed equally to this work.

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Ydens, E., Palmers, I., Hendrix, S. et al. The Next Generation of Biomarker Research in Spinal Cord Injury. Mol Neurobiol 54, 1482–1499 (2017). https://doi.org/10.1007/s12035-016-9757-x

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  • DOI: https://doi.org/10.1007/s12035-016-9757-x

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