Levels of caspase-1 in cerebrospinal fluid of patients with traumatic brain injury: correlation with intracranial pressure and outcome

Pérez-Bárcena, Jon; Crespı́, Catalina; Frontera, Guillem; Llompart‐Pou, Juan Antonio; Salazar, Osman; Goliney, Victor; Ibáñez, Javier; Bullock, M. Ross; Vaccari, Juan Pablo de Rivero

doi:10.3171/2020.2.jns193079

Cited by 20 publications

(15 citation statements)

References 22 publications

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“…Accordingly, CRP levels of less than 0.5 mg/L correspond to a low risk of disease progression, and CRP levels greater than 10 mg/L correspond to a higher risk of disease progression. 22,[33][34][35] We have recently shown that inflammasome proteins are good inflammatory biomarkers of traumatic brain injury, 16,36 stroke, 15 psoriasis, 37 and multiple sclerosis, 14 as well as mild cognitive impairment (MCI) and AD. 38 Interestingly, it has been suggested that AMD and AD share a common pathologic mechanism.…”

Section: Discussionmentioning

confidence: 99%

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Inflammasome Proteins as Inflammatory Biomarkers of Age-Related Macular Degeneration

Weaver

Cyr

Vaccari³

et al. 2020

Trans. Vis. Sci. Tech.

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Purpose Age-related macular degeneration (AMD) can result in severe vision loss and blurriness in the older population. The early and intermediate stages of AMD typically start without noticeable symptoms and can only be detected with a comprehensive eye exam. Because of the quiet onset of the disease, it is necessary to identify potential biomarkers to aid in the diagnosis, staging, and association with disease onset. Inflammasome signaling proteins are prominent biomarkers in the central nervous system, and the inflammasome has been shown to play a role in the innate inflammatory response in aging and AMD. Methods Serum from healthy controls and AMD patients were analyzed for the protein levels of Apoptosis-associated speck-like protein containing a caspase recruitment domain (ASC), interleukin (IL)-18 and C-reactive protein (CRP) to determine cutoff points, positive and negative predictive values, and receiver operator characteristic curves, as well as univariate and multivariate linear and logistic regression models. Results ASC, IL-18, and CRP were elevated in the serum of AMD patients when compared to healthy controls. The area under the curve (AUC) for ASC was 0.98 with a cutoff point of 365.6 pg/mL, whereas IL-18 had an AUC of 0.73 and a cutoff point of 242.4 pg/mL, and the AUC for CRP was 0.67 with a cutoff point of 8,684,152 pg/mL. Levels of IL-18 had a statistically significant linear correlation with that of ASC with an adjusted R 2 of 0.1906, indicating that 19% of IL-18 could be explained by ASC protein levels in serum. Moreover, a logistic regression model for the diagnosis of AMD consists of ASC and having a diagnosis of hypertension, indicating that these two factors (elevated levels of ASC and a diagnosis of hypertension [HTN]) are associated with the diagnosis of AMD. Conclusions ASC, IL-18, and CRP are elevated in patients with AMD, and the protein levels of IL-18 are partially the result of ASC protein expression. Moreover, elevated protein levels of ASC in serum and a diagnosis of HTN increase the odds of patients having a diagnosis of AMD. Translational Relevance Biomarkers of AMD may be used to monitor disease risk, response to treatment and disease progression.

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Section: Discussionmentioning

confidence: 99%

“…We have recently shown that inflammasome proteins are good inflammatory biomarkers of traumatic brain injury, 16 , 36 stroke, 15 psoriasis, 37 and multiple sclerosis, 14 as well as mild cognitive impairment (MCI) and AD. 38 Interestingly, it has been suggested that AMD and AD share a common pathologic mechanism.…”

Section: Discussionmentioning

confidence: 99%

Inflammasome Proteins as Inflammatory Biomarkers of Age-Related Macular Degeneration

Weaver

Cyr

Vaccari³

et al. 2020

Trans. Vis. Sci. Tech.

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“…We have previously shown that inflammasome signaling proteins are promising biomarkers of active inflammation in other chronic diseases and systemic injuries including stroke (Kerr et al, 2018a), traumatic brain injury (Adamczak et al, 2012;Kerr et al, 2018b;Perez-Barcena et al, 2020), multiple sclerosis (Keane et al, 2018), depression (Syed et al, 2018), mild cognitive impairment (Scott et al, 2020), and Alzheimer's disease (Scott et al, 2020). In this study, the role of the inflammasome in Ps pathogenesis was investigated through the identification of inflammasome protein levels in human serum.…”

Section: Introductionmentioning

confidence: 99%

The Inflammasome Signaling Proteins ASC and IL-18 as Biomarkers of Psoriasis

et al. 2020

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Inflammasome activation in the innate immune response plays a role in the pathogenesis of psoriasis largely due to the increased levels of pro-inflammatory cytokines. However, the precise role of inflammasomes in psoriasis (Ps) and psoriatic arthritis (PsA) is largely undefined. To establish the reliability of inflammasome signaling proteins as diagnostics and predictive biomarkers of clinical severity in this disease population, serum from healthy donors and patients with Ps/PsA were analyzed for the protein expression of caspase-1, apoptosis-associated speck-like protein containing a caspase-recruitment domain (ASC), interleukin (IL)-1b and IL-18 levels to determine cutoff points, positive and negative predictive values, and receiver operator characteristic (ROC) curves. Our data revealed that ASC and IL-18 proteins were significantly higher in the Ps group when compared to healthy controls. The area under the curve (AUC) for ASC was 0.9224 with a cutoff point of 321.8 pg/ml, while IL-18 had an AUC of 0.7818 and a cutoff point of 232.1 pg/ml. In addition, levels of IL-18 had a statistically significant linear correlation with that of ASC with an adjusted R squared of 0.2566, indicating that approximately 25% of IL-18 levels could be explained by ASC levels in serum. Our findings indicate that ASC and IL-18 play a significant role in the inflammatory response associated with the pathology of Ps. These inflammasome proteins appear to be key biomarkers in determining diagnoses in this patient population.

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“…However, inhibition of the NLRP3 inflammasome with intravenous immunoglobulin has been shown to be neuroprotective is an animal model of stroke ( Fann et al, 2013 ), and studies in NLRP3 knockout mice indicate that NLRP3 deletion results in decreased infarct volume, decreased edema and decreased permeability of the blood brain barrier ( Yang et al, 2014 ). Moreover, inflammasome proteins in humans have been shown to be reliable biomarkers of central nervous system (CNS) injury ( Adamczak et al, 2012 ; Kerr et al, 2018b ; Perez-Barcena et al, 2020 ) and disease ( Keane et al, 2018 ; Scott et al, 2020 ), including stroke ( Kerr et al, 2018a ). Thus, the inflammasome is an important regulator of the inflammatory innate immune response following stroke.…”

Section: Introductionmentioning

confidence: 99%

Netosis and Inflammasomes in Large Vessel Occlusion Thrombi

et al. 2021

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The inflammatory response appears to play a critical role in clotting in which neutrophil extracellular traps (NETs) are the major drivers of thrombosis in acute ischemic stroke (AIS). The inflammasome is an innate immune complex involved in the activation of interleukin (IL)-18 and IL-1β through caspase-1, but whether the inflammasome plays a role in NETosis in AIS remains poorly understood. Here we assessed the levels of inflammasome signaling proteins in NETs and their association with clinical and procedural outcomes of mechanical thrombectomy for AIS. Electron microscopy and immunofluorescence indicate the presence of NETs in thrombi of patients with AIS. Moreover, the inflammasome signaling proteins caspase-1 and apoptosis-associated speck-like protein containing a caspase recruitment domain (ASC) were also present in clots associated with the marker of NETosis citrullinated histone 3H (CitH3). Analysis of protein levels by a simple plex assay show that caspase-1, ASC and interleukin (IL)-1β were significantly elevated in clots when compared to plasma of AIS patients and healthy controls, while IL-18 levels were lower. Moreover, multivariate analyses show that IL-1β levels in clots contribute to the number of passes to achieve complete recanalization, and that ASC, caspase-1 and IL-18 are significant contributors to time to recanalization. Thus, inflammasome proteins are elevated in NETs present in thrombi of patients with AIS that contribute to poor outcomes following stroke.

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Levels of caspase-1 in cerebrospinal fluid of patients with traumatic brain injury: correlation with intracranial pressure and outcome

Cited by 20 publications

References 22 publications

Inflammasome Proteins as Inflammatory Biomarkers of Age-Related Macular Degeneration

Inflammasome Proteins as Inflammatory Biomarkers of Age-Related Macular Degeneration

The Inflammasome Signaling Proteins ASC and IL-18 as Biomarkers of Psoriasis

Netosis and Inflammasomes in Large Vessel Occlusion Thrombi

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