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

1
Department of Dermatology, Faculty of Medicine, University of Chile, Santiago 8380453, Chile
2
Centro Internacional de Estudios Clínicos, Probity Medical Research, Santiago 8420383, Chile
3
Dermatology Unit, San José Hospital, Santiago 8380419, Chile
4
Department of Oral Pathology, Faculty of Dentistry, Universidad Andres Bello, Santiago 8370133, Chile
5
Department of Statistics, Faculty of Dentistry, Universidad Mayor, Santiago 8320000, Chile
6
Laboratory of Periodontal Biology, Faculty of Dentistry, Universidad de Chile, Santiago 8380544, Chile
7
Department of Oral Pathology and Medicine Faculty of Dentistry, Universidad de Chile, Santiago 8380544, Chile
*
Author to whom correspondence should be addressed.
Biomolecules 2020, 10(12), 1600; https://doi.org/10.3390/biom10121600
Received: 30 September 2020 / Revised: 24 November 2020 / Accepted: 24 November 2020 / Published: 26 November 2020
(This article belongs to the Special Issue Metal Binding Proteins 2020)
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. View Full-Text
Keywords: enzymes; peptide hydrolases; metalloproteases; biomarkers; gingival crevicular fluid; atopic dermatitis enzymes; peptide hydrolases; metalloproteases; biomarkers; gingival crevicular fluid; atopic dermatitis
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MDPI and ACS Style

Valenzuela, F.; Fernández, J.; Aroca, M.; Jiménez, C.; Albers, D.; Hernández, M.; Fernández, A. Gingival Crevicular Fluid Zinc- and Aspartyl-Binding Protease Profile of Individuals with Moderate/Severe Atopic Dermatitis. Biomolecules 2020, 10, 1600. https://doi.org/10.3390/biom10121600

AMA Style

Valenzuela F, Fernández J, Aroca M, Jiménez C, Albers D, Hernández M, Fernández A. Gingival Crevicular Fluid Zinc- and Aspartyl-Binding Protease Profile of Individuals with Moderate/Severe Atopic Dermatitis. Biomolecules. 2020; 10(12):1600. https://doi.org/10.3390/biom10121600

Chicago/Turabian Style

Valenzuela, Fernando; Fernández, Javier; Aroca, Marcela; Jiménez, Constanza; Albers, Daniela; Hernández, Marcela; Fernández, Alejandra. 2020. "Gingival Crevicular Fluid Zinc- and Aspartyl-Binding Protease Profile of Individuals with Moderate/Severe Atopic Dermatitis" Biomolecules 10, no. 12: 1600. https://doi.org/10.3390/biom10121600

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