Plasma Anti-Glial Fibrillary Acidic Protein Autoantibody Levels during the Acute and Chronic Phases of Traumatic Brain Injury: A Transforming Research and Clinical Knowledge in Traumatic Brain Injury Pilot Study

Wang, Kevin; Yang, Zhihui; Yue, John K.; Zhang, Zuo‐Feng; Winkler, Ethan A.; Puccio, Ava M.; Diaz‐Arrastia, Ramon; Lingsma, Hester F.; Yuh, Esther L.; Mukherjee, Pratik; Valadka, Alex B.; Gordon, Wayne A.; Okonkwo, David O.; Manley, Geoffrey T.; Cooper, Shelly R.; Dams-O’Connor, Kristen; Hricik, Allison J.; Inoue, Tomoo; Maas, Andrew I.R.; Menon, David; Schnyer, David M.; Sinha, Tuhin; Vassar, Mary J.

doi:10.1089/neu.2015.3881

Cited by 70 publications

(56 citation statements)

References 53 publications

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“…Interestingly, higher levels of GFAP protein have been detected in the blood of patients with neurotrauma, 34 and recent studies have shown that patients with traumatic brain injury have significantly higher levels of autoantibodies against GFAP than healthy controls. 35 Together, these findings may suggest the possibility that astrocytic GFAP enters the circulation after injury to reach the peripheral organs of the immune system (e.g., spleen) where it triggers an autoimmune response culminating in the generation of anti-GFAP autoantibodies.…”

Section: Discussionmentioning

confidence: 95%

Characterization of the Antibody Response after Cervical Spinal Cord Injury

Ulndreaj

Τζέκου

Mothe

et al. 2017

Journal of Neurotrauma

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The immune system plays a critical and complex role in the pathobiology of spinal cord injury (SCI), exerting both beneficial and detrimental effects. Increasing evidence suggests that there are injury level-dependent differences in the immune response to SCI. Patients with traumatic SCI have elevated levels of circulating autoantibodies against components of the central nervous system, but the role of these antibodies in SCI outcomes remains unknown. In rodent models of mid-thoracic SCI, antibody-mediated autoimmunity appears to be detrimental to recovery. However, whether autoantibodies against the spinal cord are generated following cervical SCI (cSCI), the most common level of injury in humans, remains undetermined. To address this knowledge gap, we investigated the antibody responses following cSCI in a rat model of injury. We found increased immunoglobulin G (IgG) and IgM antibodies in the spinal cord in the subacute phase of injury (2 weeks), but not in more chronic phases (10 and 20 weeks). At 2 weeks post-cSCI, antibodies were detected at the injury epicenter and co-localized with the astroglial scar and neurons of the ventral horn. These increased levels of antibodies corresponded with enhanced activation of immune responses in the spleen. Higher counts of antibodysecreting cells were observed in the spleen of injured rats. Further, increased levels of secreted IgG antibodies and enhanced proliferation of T-cells in splenocyte cultures from injured rats were found. These findings suggest the potential development of autoantibody responses following cSCI in the rat. The impact of the post-traumatic antibody responses on functional outcomes of cSCI is a critical topic that requires further investigation.

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Section: Discussionmentioning

confidence: 95%

Characterization of the Antibody Response after Cervical Spinal Cord Injury

Ulndreaj

Τζέκου

Mothe

et al. 2017

Journal of Neurotrauma

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“…30 Single blood samples from patients with acute TBI across the full spectrum of injury severity( GCS, 3–8 [n = 25]); GCS, 9–12 [n = 8]; and GCS, 13–15 [n = 163]) were collected within 24 hours of injury. Among these patients with acute TBI, 108 (55.1%) had normal head CT (CT−) scans, while 88 (44.9%) showed CT abnormality (CT+) (Table).…”

Section: Methodsmentioning

confidence: 99%

“…Single blood samples from 21 patients with chronic TBI were collected during the inpatient rehabilitation stay (Table). 30 Sample collection and processing for the TBI and healthy control cohorts were performed identically at all sites (including the commercial vendor for controls) according to the recommendations from the National Institutes of Health–National Institute of Neurological Disorders and Stroke Common Data Elements Biospecimens and Biomarkers Working Group 31 (eMethods in the Supplement provides details). Plasma was extracted after centrifugation of whole blood collected in K2-EDTA blood tubes for 5 minutes at 3000 g .…”

Section: Methodsmentioning

confidence: 99%

Comparing Plasma Phospho Tau, Total Tau, and Phospho Tau–Total Tau Ratio as Acute and Chronic Traumatic Brain Injury Biomarkers

et al. 2017

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IMPORTANCEAnnually in the United States, at least 3.5 million people seek medical attention for traumatic brain injury (TBI). The development of therapies for TBI is limited by the absence of diagnostic and prognostic biomarkers. Microtubule-associated protein tau is an axonal phosphoprotein. To date, the presence of the hypophosphorylated tau protein (P-tau) in plasma from patients with acute TBI and chronic TBI has not been investigated. OBJECTIVETo examine the associations between plasma P-tau and total-tau (T-tau) levels and injury presence, severity, type of pathoanatomic lesion (neuroimaging), and patient outcomes in acute and chronic TBI. DESIGN, SETTING, AND PARTICIPANTSIn the TRACK-TBI Pilot study, plasma was collected at a single time point from 196 patients with acute TBI admitted to 3 level I trauma centers (<24 hours after injury) and 21 patients with TBI admitted to inpatient rehabilitation units (mean [SD], 176.4 [44.5] days after injury). Control samples were purchased from a commercial vendor. The TRACK-TBI Pilot study was conducted from April 1, 2010, to June 30, 2012. Data analysis for the current investigation was performed from August 1, 2015, to March 13, 2017.MAIN OUTCOMES AND MEASURES Plasma samples were assayed for P-tau (using an antibody that specifically recognizes phosphothreonine-231) and T-tau using ultra-high sensitivity laser-based immunoassay multi-arrayed fiberoptics conjugated with rolling circle amplification. RESULTSIn the 217 patients with TBI, 161 (74.2%) were men; mean (SD) age was 42.5 (18.1) years. The P-tau and T-tau levels and P-tau-T-tau ratio in patients with acute TBI were higher than those in healthy controls. Receiver operating characteristic analysis for the 3 tau indices demonstrated accuracy with area under the curve (AUC) of 1.000, 0.916, and 1.000, respectively, for discriminating mild TBI (Glasgow Coma Scale [GCS] score, 13-15, n = 162) from healthy controls. The P-tau level and P-tau-T-tau ratio were higher in individuals with more severe TBI (GCS, Յ12 vs 13-15). The P-tau level and P-tau-T-tau ratio outperformed the T-tau level in distinguishing cranial computed tomography-positive from -negative cases (AUC = 0.921, 0.923, and 0.646, respectively). Acute P-tau levels and P-tau-T-tau ratio weakly distinguished patients with TBI who had good outcomes (Glasgow Outcome Scale-Extended GOS-E, 7-8) (AUC = 0.663 and 0.658, respectively) and identified those with poor outcomes (GOS-E, Յ4 vs >4) (AUC = 0.771 and 0.777, respectively). Plasma samples from patients with chronic TBI also showed elevated P-tau levels and a P-tau-T-tau ratio significantly higher than that of healthy controls, with both P-tau indices strongly discriminating patients with chronic TBI from healthy controls (AUC = 1.000 and 0.963, respectively).CONCLUSIONS AND RELEVANCE Plasma P-tau levels and P-tau-T-tau ratio outperformed T-tau level as diagnostic and prognostic biomarkers for acute TBI. Compared with T-tau levels alone, P-tau levels and P-tau-T-tau ratios show more robust and sustained el...

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“…When the sera of severe TBI patients were screened using brain immunoblots, a significant increase in the amount of GFAP-specific antibodies was detected beginning at day 5 after TBI (Zhang et al, 2014). The concentrations of GFAP-specific autoantibodies were found to be significantly higher in TBI patients compared with healthy controls at 6 months after injury (Wang et al, 2016). In addition, autoantibodies against S100β were detected in the serum of football players during season (Marchi et al, 2013).…”

Section: Biomarkersmentioning

confidence: 99%

Biomarkers of Traumatic Brain Injury: Temporal Changes in Body Fluids

Harel¹,

Kvist²,

Salla³

et al. 2016

eNeuro

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Traumatic brain injuries (TBIs) are caused by a hit to the head or a sudden acceleration/deceleration movement of the head. Mild TBIs (mTBIs) and concussions are difficult to diagnose. Imaging techniques often fail to find alterations in the brain, and computed tomography exposes the patient to radiation. Brain-specific biomolecules that are released upon cellular damage serve as another means of diagnosing TBI and assessing the severity of injury. These biomarkers can be detected from samples of body fluids using laboratory tests. Dozens of TBI biomarkers have been studied, and research related to them is increasing. We reviewed the recent literature and selected 12 biomarkers relevant to rapid and accurate diagnostics of TBI for further evaluation. The objective was especially to get a view of the temporal profiles of the biomarkers’ rise and decline after a TBI event. Most biomarkers are rapidly elevated after injury, and they serve as diagnostics tools for some days. Some biomarkers are elevated for months after injury, although the literature on long-term biomarkers is scarce. Clinical utilization of TBI biomarkers is still at a very early phase despite years of active research.

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Plasma Anti-Glial Fibrillary Acidic Protein Autoantibody Levels during the Acute and Chronic Phases of Traumatic Brain Injury: A Transforming Research and Clinical Knowledge in Traumatic Brain Injury Pilot Study

Cited by 70 publications

References 53 publications

Characterization of the Antibody Response after Cervical Spinal Cord Injury

Characterization of the Antibody Response after Cervical Spinal Cord Injury

Comparing Plasma Phospho Tau, Total Tau, and Phospho Tau–Total Tau Ratio as Acute and Chronic Traumatic Brain Injury Biomarkers

Biomarkers of Traumatic Brain Injury: Temporal Changes in Body Fluids

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