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

Abstract

Atopic dermatitis (AD) is a protease-modulated chronic disorder with heterogenous clinical manifestations which may lead to an imprecise diagnosis. So far, there are no diagnostic protease tests for AD. We explored the gingival crevicular fluid (GCF) protease profile of periodontally-healthy individuals with moderate/severe AD compared to healthy controls. An exploratory case-control study was conducted. Matching AD patients (n=6) and controls (n=6) 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. The GCF levels of zinc-binding ADAM8, ADAM9, MMP8 and Neprilysin/CD10, aspartyl-binding Cathepsin E, and 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 MMP-8+ADAMP-9 was 0.90. In conclusion, differences in the protease profile between AD and control patients associated with MMP8, Cathepsin E and ADAM9. MMP8, ADAM9 and Cathepsin E may be useful as combined diagnostic and therapeutic biomarkers of moderate/severe AD.

Flare management in atopic dermatitis: from definition to treatment

“…Dysregulation in the protease activity in the skin may also be relevant to the deterioration of the epidermal barrier in the premenstrual phase in women with AD. 51 – 53 The same hormonal influences may be involved in AD exacerbation or flares during pregnancy. 54 …”

“…Alteration of skin microbiota [16][17][18][19][20][21][22][23][24][25][26] Exposure to allergens 27,28 Skin barrier dysfunction [29][30][31][32][33] Food allergy 34 Dysregulation of cytokine production [29][30][31][34][35][36][37] Hot and humid environment 38,39 Stressful life events 38,[40][41][42][43][44][45][46][47] Dry and cold environment 38,48 Hormonal changes (premenstrual phase, pregnancy) [49][50][51][52][53][54] Sweating (physical exercise) 38 Sun exposure 55,56 Clothing with irritating fibers (wool) 57 Eczema herpeticum, caused by the herpes simpl...…”

Classifying atopic dermatitis: a systematic review of phenotypes and associated characteristics

“…Regarding WHO region, the majority of studies were conducted in the European Region ( n = 50, 55%), followed by the Western Pacific Region ( n = 21, 23%), the Region of the Americas ( n = 16, 18%) and the African Region and the Eastern Mediterranean Region (both n = 1, 1%). Investigated characteristics included the following categories: skin barrier function ( n = 15), 19–33 serum blood cell types and markers ( n = 23), 9,18,23,34–53 serum Ig levels and sensitization ( n = 15), 20,22,25,51,54–64 microbial colonization ( n = 10), 15,65–73 DNA mutations ( n = 14), 10,51,74–85 skin parameters ( n = 8), 32,86–92 personal and family history of allergy ( n = 4), 58,93–95 comorbidities ( n = 7), 8,51,96–100 morphology ( n = 3) 51,93,101 and other characteristics ( n = 5) 51,95,102–104 (see Table a and Appendix , Supporting Information).…”

Identification of IL-18 and Soluble Cell Adhesion Molecules in the Gingival Crevicular Fluid as Novel Biomarkers of Psoriasis

“…In that study, sE-selectin showed a 0.646 and 0.704 area under the ROC curve for the detection leukoplakia and OSCC, respectively [ 57 ]. Detecting biomarkers in the GCF has the advantage of being a less invasive, safe, and rapid method [ 13 , 30 ]. Thus, IL-18 and sE-selectin appear to be promising biomarkers for screening and diagnosis of psoriasis, helping clinicians make their early diagnosis.…”

“…The GCF is used as a biological source of biomarkers to study periodontal and systemic diseases [ 27 , 28 ]. Recently, we reported downregulation of MMP-8 and overexpression of S100A8 in the GCF of patients with atopic dermatitis and psoriasis, respectively, independent of the patient’s periodontal status, indicating that MMP-8 and S100A8 proteins could be used as diagnostic biomarkers of these diseases, respectively [ 29 , 30 ]. Therefore, we hypothesize that psoriasis can modify the concentration of inflammatory biomarkers in the GCF.…”