Serum levels of ubiquitin C-terminal hydrolase distinguish mild traumatic brain injury from trauma controls and are elevated in mild and moderate traumatic brain injury patients with intracranial lesions and neurosurgical intervention

Papa, Linda; Lewis, Lawrence M.; Silvestri, Salvatore; Falk, Jay L.; Giordano, Philip; Brophy, Gretchen M.; Demery, Jason A.; Liu, Ming Cheng; Mo, Jixiang; Akinyi, Linnet; Mondello, Stefania; Schmid, Kara; Robertson, Claudia S.; Tortella, Frank C.; Hayes, Ronald L.; Wang, Kevin

doi:10.1097/ta.0b013e3182491e3d

Cited by 203 publications

(180 citation statements)

References 39 publications

(34 reference statements)

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“…141 The neuron-specific protein UCH-L1 (ubiquitin carboxyl-terminal hydrolase isozyme L1) was first linked to neurodegenerative pathology through its involvement in PD, 142 and its presence in serum was later identified as a biomarker for severe TBI. [143][144][145] Serum levels of UCH-L1 may have diagnostic utility in concussion, 146 but recent evidence suggests a lack of correlation between elevated serum levels and subconcussive hits. 147 The clinical utility of UCH-L1 in paediatric populations warrants further study.…”

Section: Fluid-based Biomarkersmentioning

confidence: 99%

Mind the gaps—advancing research into short-term and long-term neuropsychological outcomes of youth sports-related concussions

et al. 2015

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Section: Fluid-based Biomarkersmentioning

confidence: 99%

Mind the gaps—advancing research into short-term and long-term neuropsychological outcomes of youth sports-related concussions

et al. 2015

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“…Because we previously identified a dominant autoantibody response to glial intermediate filament protein GFAP among patients with severe TBI, 26,[33][34][35] here we sought to expand these findings by using the TRACK-TBI pilot study cohorts and plasma samples. 1,36,37 Of 586 subjects with acute TBI from the TRACK-TBI pilot, we identified 196 with available acute plasma samples (collected within 24 h of injury) for this autoantibody study.…”

Section: Anti-gfap Autoantibody Levels In Acute Plasma Samples From Tmentioning

confidence: 99%

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

Yang

Yue

et al. 2016

Journal of Neurotrauma

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We described recently a subacute serum autoantibody response toward glial fibrillary acidic protein (GFAP) and its breakdown products 5-10 days after severe traumatic brain injury (TBI). Here, we expanded our anti-GFAP autoantibody (AutoAb[GFAP]) investigation to the multicenter observational study Transforming Research and Clinical Knowledge in TBI Pilot (TRACK-TBI Pilot) to cover the full spectrum of TBI (Glasgow Coma Scale 3-15) by using acute (<24 h) plasma samples from 196 patients with acute TBI admitted to three Level I trauma centers, and a second cohort of 21 participants with chronic TBI admitted to inpatient TBI rehabilitation. We find that acute patients self-reporting previous TBI with loss of consciousness (LOC) (n = 43) had higher day 1 AutoAb[GFAP] (mean -standard error: 9.11 -1.42; n = 43) than healthy controls (2.90 -0.92; n = 16; p = 0.032) and acute patients reporting no previous TBI (2.97 -0.37; n = 106; p < 0.001), but not acute patients reporting previous TBI without LOC (8.01 -1.80; n = 47; p = 0.906). These data suggest that while exposure to TBI may trigger the AutoAb[GFAP] response, circulating antibodies are elevated specifically in acute TBI patients with a history of TBI. AutoAb[GFAP] levels for participants with chronic TBI (average post-TBI time 176 days or 6.21 months) were also significantly higher (15.08 -2.82; n = 21) than healthy controls ( p < 0.001). These data suggest a persistent upregulation of the autoimmune response to specific brain antigen(s) in the subacute to chronic phase after TBI, as well as after repeated TBI insults. Hence, AutoAb[GFAP] may be a sensitive assay to study the dynamic interactions between postinjury brain and patient-specific autoimmune responses across acute and chronic settings after TBI.

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“…Some of the protein biomarkers that have been used are S100b, NSE, glial fibrillary acidic protein (and its breakdown products), ubiquitin carboxyl-terminal esterase L1, and C-tau. 18,[74][75][76][77][78][79][80][81][82] However, there are issues in the use of these proteins for assessing TBI, which includes sensitivity and specificity, use in adult versus pediatric patients, lack of correlation between the values in blood and CSF, and lack of correlation with the different levels of TBI severity.…”

Section: Rubenstein Et Almentioning

confidence: 99%

A Novel, Ultrasensitive Assay for Tau: Potential for Assessing Traumatic Brain Injury in Tissues and Biofluids

Rubenstein

Chang

Davies

et al. 2015

Journal of Neurotrauma

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Traumatic brain injury (TBI) is a cause of death and disability and can lead to tauopathy-related dementia at an early age. Pathologically, TBI results in axonal injury that is coupled to tau hyperphosphorylation, leading to microtubule instability and tau-mediated neurodegeneration. This suggests that the forms of this protein might serve as neuroinjury-related biomarkers for diagnosis of injury severity and prognosis of the neurological damage prior to clinical expression. We initially determined whether we could detect tau in body fluids using a highly sensitive assay. We used a novel immunoassay, enhanced immunoassay using multi-arrayed fiberoptics (EIMAF) either alone or in combination with rolling circle amplification (a-EIMAF) for the detection of total (T) and phosphorylated (P) tau proteins from brains and biofluids (blood, CSF) of rodents following controlled cortical impact (CCI) and human patients post severe TBI (sTBI). This assay technology for tau is the most sensitive to date with a detection limit of approximately 100 ag/mL for either T-tau and Ptau. In the rodent models, T-tau and P-tau levels in brain and blood increased following CCI during the acute phase and remained high during the chronic phase (30 d). In human CSF samples, T-tau and P-tau increased during the sampling period (5-6 d). T-tau and P-tau in human serum rose during the acute phase and decreased during the chronic stage but was still detectable beyond six months post sTBI. Thus, EIMAF has the potential for assessing both the severity of the proximal injury and the prognosis using easily accessible samples.

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Serum levels of ubiquitin C-terminal hydrolase distinguish mild traumatic brain injury from trauma controls and are elevated in mild and moderate traumatic brain injury patients with intracranial lesions and neurosurgical intervention

Cited by 203 publications

References 39 publications

Mind the gaps—advancing research into short-term and long-term neuropsychological outcomes of youth sports-related concussions

Mind the gaps—advancing research into short-term and long-term neuropsychological outcomes of youth sports-related concussions

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

A Novel, Ultrasensitive Assay for Tau: Potential for Assessing Traumatic Brain Injury in Tissues and Biofluids

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