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Gingival Crevicular Fluid Zinc- and Aspartyl-Binding Protease Profile of Individuals with Moderate/Severe Atopic Dermatitis

Atopic dermatitis (AD) is a protease-modulated chronic disorder with heterogenous clinical manifestations which may lead to an imprecise diagnosis. To date, there are no diagnostic protease tests for AD. We explored the gingival crevicular fluid (GCF) protease profile of individuals with moderate/se...

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Autores principales: Valenzuela, Fernando, Fernández, Javier, Aroca, Marcela, Jiménez, Constanza, Albers, Daniela, Hernández, Marcela, Fernández, Alejandra
Formato: Online Artículo Texto
Lenguaje:English
Publicado: MDPI 2020
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7761491/
https://www.ncbi.nlm.nih.gov/pubmed/33255937
http://dx.doi.org/10.3390/biom10121600
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author Valenzuela, Fernando
Fernández, Javier
Aroca, Marcela
Jiménez, Constanza
Albers, Daniela
Hernández, Marcela
Fernández, Alejandra
author_facet Valenzuela, Fernando
Fernández, Javier
Aroca, Marcela
Jiménez, Constanza
Albers, Daniela
Hernández, Marcela
Fernández, Alejandra
author_sort Valenzuela, Fernando
collection PubMed
description Atopic dermatitis (AD) is a protease-modulated chronic disorder with heterogenous clinical manifestations which may lead to an imprecise diagnosis. To date, there are no diagnostic protease tests for AD. We explored the gingival crevicular fluid (GCF) protease profile of individuals with moderate/severe AD compared to healthy controls. An exploratory case-control study was conducted. AD patients (n = 23) and controls (n = 21) were enrolled at the International Center for Clinical Studies, Santiago, Chile. Complete dermatological and periodontal evaluations (involving the collection of GCF samples) were made. The levels of 35 proteases were analyzed using a human protease antibody array in matching AD patients (n = 6) and controls (n = 6) with healthy periodontium. The GCF levels of zinc-binding ADAM8, ADAM9, MMP8, Neprilysin/CD10, aspartyl-binding Cathepsin E, serin-binding Protein convertase9, and uPA/Urokinase proteases were lower in moderate/severe AD patients compared to controls (p < 0.05). No inter-group differences in the levels of the other 28 proteases were found. MMP8, Cathepsin E, and ADAM9 were the biomarkers with the highest sensitivity and specificity regarding the detection of AD (p < 0.05). The area under receiver operating characteristic (ROC) curve for MMP8 was 0.83 and MMP8 + ADAMP9 was 0.90, with no significant differences (p = 0.132). A combined model of MMP8, Cathepsin E, and ADAM9 was not considered since it did not converge. Then, levels of MMP8 in GCF were determined using a multiplex bead immunoassay in 23 subjects with AD and 21 healthy subjects. Lower levels of MMP8 in the GCF from the AD group versus healthy group (p = 0.029) were found. This difference remained significant after adjustment by periodontitis (p = 0.042). MMP8 revealed the diagnostic potential to identify AD patients versus healthy controls, (ROC area = 0.672, p < 0.05). In conclusion, differences in the protease profile between AD and control patients were associated with MMP8, Cathepsin E, and ADAM9. Based on the multiplex assay results, MMP8 was lower in AD patients than controls, suggesting that MMP8 may be a diagnostic biomarker candidate.
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spelling pubmed-77614912020-12-26 Gingival Crevicular Fluid Zinc- and Aspartyl-Binding Protease Profile of Individuals with Moderate/Severe Atopic Dermatitis Valenzuela, Fernando Fernández, Javier Aroca, Marcela Jiménez, Constanza Albers, Daniela Hernández, Marcela Fernández, Alejandra Biomolecules Communication Atopic dermatitis (AD) is a protease-modulated chronic disorder with heterogenous clinical manifestations which may lead to an imprecise diagnosis. To date, there are no diagnostic protease tests for AD. We explored the gingival crevicular fluid (GCF) protease profile of individuals with moderate/severe AD compared to healthy controls. An exploratory case-control study was conducted. AD patients (n = 23) and controls (n = 21) were enrolled at the International Center for Clinical Studies, Santiago, Chile. Complete dermatological and periodontal evaluations (involving the collection of GCF samples) were made. The levels of 35 proteases were analyzed using a human protease antibody array in matching AD patients (n = 6) and controls (n = 6) with healthy periodontium. The GCF levels of zinc-binding ADAM8, ADAM9, MMP8, Neprilysin/CD10, aspartyl-binding Cathepsin E, serin-binding Protein convertase9, and uPA/Urokinase proteases were lower in moderate/severe AD patients compared to controls (p < 0.05). No inter-group differences in the levels of the other 28 proteases were found. MMP8, Cathepsin E, and ADAM9 were the biomarkers with the highest sensitivity and specificity regarding the detection of AD (p < 0.05). The area under receiver operating characteristic (ROC) curve for MMP8 was 0.83 and MMP8 + ADAMP9 was 0.90, with no significant differences (p = 0.132). A combined model of MMP8, Cathepsin E, and ADAM9 was not considered since it did not converge. Then, levels of MMP8 in GCF were determined using a multiplex bead immunoassay in 23 subjects with AD and 21 healthy subjects. Lower levels of MMP8 in the GCF from the AD group versus healthy group (p = 0.029) were found. This difference remained significant after adjustment by periodontitis (p = 0.042). MMP8 revealed the diagnostic potential to identify AD patients versus healthy controls, (ROC area = 0.672, p < 0.05). In conclusion, differences in the protease profile between AD and control patients were associated with MMP8, Cathepsin E, and ADAM9. Based on the multiplex assay results, MMP8 was lower in AD patients than controls, suggesting that MMP8 may be a diagnostic biomarker candidate. MDPI 2020-11-26 /pmc/articles/PMC7761491/ /pubmed/33255937 http://dx.doi.org/10.3390/biom10121600 Text en © 2020 by the authors. Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (http://creativecommons.org/licenses/by/4.0/).
spellingShingle Communication
Valenzuela, Fernando
Fernández, Javier
Aroca, Marcela
Jiménez, Constanza
Albers, Daniela
Hernández, Marcela
Fernández, Alejandra
Gingival Crevicular Fluid Zinc- and Aspartyl-Binding Protease Profile of Individuals with Moderate/Severe Atopic Dermatitis
title Gingival Crevicular Fluid Zinc- and Aspartyl-Binding Protease Profile of Individuals with Moderate/Severe Atopic Dermatitis
title_full Gingival Crevicular Fluid Zinc- and Aspartyl-Binding Protease Profile of Individuals with Moderate/Severe Atopic Dermatitis
title_fullStr Gingival Crevicular Fluid Zinc- and Aspartyl-Binding Protease Profile of Individuals with Moderate/Severe Atopic Dermatitis
title_full_unstemmed Gingival Crevicular Fluid Zinc- and Aspartyl-Binding Protease Profile of Individuals with Moderate/Severe Atopic Dermatitis
title_short Gingival Crevicular Fluid Zinc- and Aspartyl-Binding Protease Profile of Individuals with Moderate/Severe Atopic Dermatitis
title_sort gingival crevicular fluid zinc- and aspartyl-binding protease profile of individuals with moderate/severe atopic dermatitis
topic Communication
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7761491/
https://www.ncbi.nlm.nih.gov/pubmed/33255937
http://dx.doi.org/10.3390/biom10121600
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