TY - JOUR
T1 - Inflammasome proteins as inflammatory biomarkers of age-related macular degeneration
AU - Weaver, Cailey
AU - Cyr, Brianna
AU - de Rivero Vaccari, Juan Carlos
AU - de Rivero Vaccari, Juan Pablo
N1 - Publisher Copyright:
© 2020 The Authors.
PY - 2020
Y1 - 2020
N2 - 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 R2 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.
AB - 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 R2 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.
KW - ASC, IL-18
KW - Biomarkers
KW - Inflammasome
KW - Macular degeneration
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U2 - 10.1167/tvst.9.13.27
DO - 10.1167/tvst.9.13.27
M3 - Article
C2 - 33364081
AN - SCOPUS:85098049609
VL - 9
SP - 1
EP - 9
JO - Translational Vision Science and Technology
JF - Translational Vision Science and Technology
SN - 2164-2591
IS - 13
M1 - 27
ER -