A point‐of‐care test of active matrix metalloproteinase‐8 predicts triggering receptor expressed on myeloid cells‐1 (TREM‐1) levels in saliva

Abstract

Background This cross‐sectional study aims to investigate if a point‐of‐care (PoC) test of active matrix metalloproteinase‐8 (aMMP‐8) predicts levels of inflammation amplifier triggering receptor expressed on myeloid cells‐1 (TREM‐1) and its putative ligand the neutrophil peptidoglycan recognition protein 1 (PGLYRP1) in saliva. Methods Forty‐seven adolescents, aged 15 to 17 years, were tested with aMMP‐8 PoC test, which was followed by a full‐mouth clinical examination of the assessment of periodontal, mucosal, and oral health. TREM‐1 and PGLYRP1 levels were analyzed by ELISA. The immunofluorometric assay (IFMA) specific for aMMP‐8 was used as the reference method. Results Fourteen saliva samples out of a total of 47 showed positivity for aMMP‐8 PoC test. Both the TREM‐1 and the aMMP‐8 (IFMA) levels were significantly elevated among the aMMP‐8 PoC test positives compared with the PoC test negatives (P < 0.05). Moreover, aMMP‐8 levels assessed by IFMA showed a strong positive correlation with TREM‐1 levels in saliva (r = 0.777, P < 0.001). The number of sites with a probing depth of ≥4 mm was significantly lower among the adolescents that had a negative aMMP‐8 PoC test result, and TREM‐1 levels < 75 pg/mL (P < 0.05). In contrast, adolescents with a positive aMMP‐8 PoC test result (i.e., elevated aMMP‐8 levels) together with elevated TREM‐1 levels had a significantly higher number of periodontal pockets with ≥4 mm (P < 0.001). Conclusion The present study validated usability of aMMP‐8 PoC test for predicting “proinflammatory” salivary profile and periodontal health status in adolescents.

On the diagnostic discrimination ability of mouthrinse and salivary aMMP-8 point-of-care testing regarding periodontal health and disease

“…1 illustrates the ability of aMMP-8 PoC mouthrinse test compared to aMMP-8 IFMA measured from saliva, and it clearly shows how saliva is inferior to mouthrinse in aMMP-8 measurements related to identifying periodontal health and disease. There is a significant association between the aMMP-8 PoC mouthrinse test result and aMMP-8 IFMA levels in saliva in this sample of adolescents, as has been shown recently by Räisänen et al (2019b). However, if patient's periodontal health is considered, the distinction of salivary aMMP-8 IFMA measurements is far from perfect between a positive and negative test result.…”

Active MMP-8 (aMMP-8) as a Grading and Staging Biomarker in the Periodontitis Classification

“…Our findings indicate that the aMMP-8 mouthrinse PoC/chairside test [10,12,[14][15][16][17][18][19][20][21][22][23][24][25][26] can be implemented as the staging and grading biomarker in the new classification system of periodontitis [1]. In this regard, a previous study by Räisänen et al [21] showed that mouthrinse aMMP-8 measurements are better and more precise in identifying periodontal health and disease among adolescents in comparison to saliva aMMP-8 measurements.…”

“…A.G. performed a full-mouth clinical examination for each patient to assess their periodontal and oral health, after which each patient's aMMP-8 mouthrinse test result was read. Firstly, aMMP-8 levels in mouthrinse were significantly lower among healthy patients compared with patients in more severe periodontitis stages and grades (Kruskal-Wallis test, p < 0.01; Figure 1), as would be expected from an effective diagnostic tool to classify periodontal health and disease [14][15][16][17][18][19][20][21][22][23][24][25][26]. This result is also in agreement with previous studies that have shown that aMMP-8 predicts very well future periodontal breakdown (positive predictive values range between 81.8%-94.7%) [35].…”

“…Furthermore, active periodontal tissue destruction in progress (i.e., the active phase of periodontal disease) can be identified non-invasively in oral fluids as a pathological elevation of aMMP-8 levels [11][12][13]. Thus, it is no surprise that the aMMP-8 chairside/point-of-care (PoC) oral fluid tests have continuously been successful in identifying active periodontal tissue destruction and active periodontal disease (periodontitis, peri-implantitis, subclinical periodontitis) among adults and adolescents of different ethnic populations [10,12,[14][15][16][17][18][19][20][21][22][23][24][25][26]. Similarly, previous longitudinal studies have shown that aMMP-8 assays with the same antibody can be used for predicting the progression of periodontitis and attachment loss, and monitoring treatment of periodontitis during the maintenance phase [27][28][29][30][31][32][33][34].…”

“…We propose aMMP-8 as the biomarker and the aMMP-8 PoC/chairside mouthrinse testing to be incorporated into the new periodontal disease classification system by Tonetti et al [1] (see Table 2: modified from Tonetti et al [1]), to improve the diagnostic accuracy of periodontal diseases and their progression. The proposed aMMP-8 measurements by an aMMP-8 PoC mouthrinse test with a cut-off of 20 ng/mL allows this risk to be measured early enough, effectively and non-invasively in clinical practice within 5 min without the need to use laborious and time-consuming laboratory equipment [10,12,[14][15][16][17][18][19][20][21][22][23][24][25][26]. The ability to identify active periods of periodontitis (=ongoing periodontal breakdown) chairside and in real-time is of great value to dentists trying to optimize patient treatment.…”