Diagnostic Value of Serum Levels of GFAP, pNF-H, and NSE Compared With Clinical Findings in Severity Assessment of Human Traumatic Spinal Cord Injury

Ahadi, Reza; Khodagholi, Fariba; Daneshi, Abdolhadi; Vafaei, Ali; Mafi, Amirali; Jorjani, Masoumeh

doi:10.1097/brs.0000000000000654

Cited by 72 publications

(61 citation statements)

References 36 publications

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“…[16,17] Previous studies have reported that GFAP can be detected in the serum of SCI patients where it can elicit an immune response. [18] Alternatively, an immune response could have been initiated within the injured spinal cord itself where the blood-spinal cord barrier is disrupted and the concentration of released GFAP/GFAP breakdown products are likely to be substantially higher. Another limitation of the current study is that the consequences of autoantibody production on outcome have not been investigated.…”

Section: Discussionmentioning

confidence: 99%

Identification of autoantibodies to glial fibrillary acidic protein in spinal cord injury patients

Hergenroeder

Moore²,

Schmitt

et al. 2016

NeuroReport

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Traumatic spinal cord injury (SCI) is a devastating injury causing significant morbidity and mortality. Experimental studies have demonstrated that SCI induced cellular damage and disruption of the blood-spinal cord-barrier can initiate an autoimmune response. This response is thought to be pathogenic and contribute to poor outcome. The objective of this research was to investigate whether human SCI mounts an autoimmune response to self-antigens. Plasma samples were collected longitudinally from SCI patients (n=18) at acute (T1, <48 hr) and subacute (T2, 2-4 wk) time points to probe western blots of human brain homogenates in order to screen patients for the presence of putative autoantibodies. To identify the corresponding antigens, 2-dimensional (2D) gel electrophoresis, western blot and liquid chromatography coupled with mass spectrometry (LC-MS/MS) analyses were performed. We found that 4 of 18 patients (22%) had novel immunoreactive bands ranging in size from 36-42 kDa present in subacute, but not in acute, plasma samples suggesting post-injury production. To identify the cross-reacting antigens, we separated brain proteins by 2D gel electrophoresis and identified 9 immunoreactive spots. Amino acid sequence analysis of these spots identified peptides that mapped to glial fibrillary acidic protein (GFAP). Our results suggest that approximately 22% of SCI patients generated autoantibodies to GFAP. Future studies will be required to determine if these autoantibodies contribute to the pathogenic sequelae of SCI.

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Section: Discussionmentioning

confidence: 99%

Identification of autoantibodies to glial fibrillary acidic protein in spinal cord injury patients

Hergenroeder

Moore²,

Schmitt

et al. 2016

NeuroReport

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“…49,50 Consistent with this, it has been previously reported that GFAP, as well as other CNS proteins, can be detected in plasma of SCI patients. [51][52][53] Once in the bloodstream, proteins released from the CNS can serve as antigens to trigger a B-cell response and generation of immunoglobulins (i.e., IgGs). Alternatively, the infiltration of immune cells into the damaged cord may allow these cells to contact locally released GFAP, thereby eliciting an immune response.…”

Section: Discussionmentioning

confidence: 99%

Increased Levels of Circulating Glial Fibrillary Acidic Protein and Collapsin Response Mediator Protein-2 Autoantibodies in the Acute Stage of Spinal Cord Injury Predict the Subsequent Development of Neuropathic Pain

Hergenroeder

Redell

Choi

et al. 2018

Journal of Neurotrauma

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Neuropathic pain develops in 40-70% of spinal cord injury (SCI) patients and markedly compromises quality of life. We examined plasma from SCI patients for autoantibodies to glial fibrillary acidic protein (GFAP) and collapsin response mediator protein-2 (CRMP2) and evaluated their relationship to the development of neuropathic pain. In study 1, plasma samples and clinical data from 80 chronic SCI patients (1-41 years post-SCI) were collected and screened for GFAP autoantibodies (GFAPab). Results from study 1 indicated that GFAPab were present in 34 of 80 (42.5%) patients, but circulating levels did not correlate with the occurrence of neuropathic pain. In study 2, longitudinal plasma samples and clinical data were collected from 38 acute SCI patients. The level of GFAPab measured at 16 ± 7 days post-SCI was found to be significantly higher in patients that subsequently developed neuropathic pain (within 6 months post-SCI) than patients who did not (T = 219; p = 0.02). In study 3, we identified CRMP2 as an autoantibody target (CRMP2ab) in 23% of acute SCI patients. The presence of GFAPab and/or CRMP2ab increased the odds of subsequently developing neuropathic pain within 6 months of injury by 9.5 times (p = 0.006). Our results suggest that if a causal link can be established between these autoantibodies and the development of neuropathic pain, strategies aimed at reducing the circulating levels of these autoantibodies may have therapeutic value.

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“…The levels of NSE within CSF in a cohort of 16 SCI patients were increased and correlated with the baseline neurologic impairment being either motor complete (AIS A and B) or motor incomplete (AIS C and D) [18]. Ahadi et al (2015) recently found that also serum NSE levels were significantly higher during the first 48 hours after injury in the 26 traumatic SCI patients included in the study compared to the control group [19]. In a population of 34 patients with vertebral spine fractures, however, the analysis of NSE levels revealed no significant difference [20].…”

Section: Neuron-derived Biomarkersmentioning

confidence: 98%

The Next Generation of Biomarker Research in Spinal Cord Injury

et al. 2016

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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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Diagnostic Value of Serum Levels of GFAP, pNF-H, and NSE Compared With Clinical Findings in Severity Assessment of Human Traumatic Spinal Cord Injury

Abstract: 2.

Cited by 72 publications

References 36 publications

Identification of autoantibodies to glial fibrillary acidic protein in spinal cord injury patients

Identification of autoantibodies to glial fibrillary acidic protein in spinal cord injury patients

Increased Levels of Circulating Glial Fibrillary Acidic Protein and Collapsin Response Mediator Protein-2 Autoantibodies in the Acute Stage of Spinal Cord Injury Predict the Subsequent Development of Neuropathic Pain

The Next Generation of Biomarker Research in Spinal Cord Injury

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