Accuracy of single molecular biomarkers in gingival crevicular fluid for the diagnosis of periodontitis: A systematic review and meta‐analysis

Abstract

Aim To analyse, by means of a meta‐analytical approach, the diagnostic accuracy of molecular biomarkers in gingival crevicular fluid (GCF) for the detection of periodontitis in systemically healthy subjects. Material and Methods Studies on GCF molecular biomarkers providing a binary classification table (or sensitivity and specificity values and group sample sizes) in individuals with clinically diagnosed periodontitis were considered eligible. The search was performed using six electronic databases. The methodological quality of studies was assessed through the tool Quality Assessment of Diagnostic Studies. Meta‐analyses were performed using the Hierarchical Summary Receiver Operating Characteristic, which adjusts classification data using random effects logistic regression. Results The included papers identified 36 potential biomarkers for the detection of periodontitis and for four of them meta‐analyses were performed. The median sensitivity and specificity were for MMP8, 76.7% and 92.0%; for elastase, 74.6% and 81.1%; for cathepsin, 72.8% and 67.3%, respectively. The worst estimates of sensitivity and specificity were for trypsin (71.3% and 66.1%, respectively). Conclusions MMP8 showed good sensitivity and excellent specificity, which resulted in this biomarker being clinically the most useful or effective for the diagnosis of periodontitis in systemically healthy subjects, regardless of smoking condition.

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

“…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]. Secondly, BOP and VPI levels were also associated with the periodontitis stage and grade (Kruskal-Wallis test, p < 0.01); Figure 1), but these two parameters were also moderately correlated with each other (Spearman's rho = 0.586, p < 0.001).…”

“…Many other potential biomarkers to detect periodontitis and related systemic diseases have been investigated as well [35][36][37][38][39][40][41][42][43]; these include, along with others, asymmetric dimethylarginine (ADMA), C-reactive protein, interferon gamma (IFN-γ), interleukin-6 (IL-6), macrophage inflammatory protein-1α (MIP-1α), PMN elastase, vitamin C and also antioxidants [35][36][37][38][39][40][41][42][43]. For example, vitamin C is linked to oxidative MMP-activation cascade by its recorded ability to prevent the oxidative activation of proMMP-8 [44].…”

“…For example, vitamin C is linked to oxidative MMP-activation cascade by its recorded ability to prevent the oxidative activation of proMMP-8 [44]. According to a recent systematic review, aMMP-8/MMP-8 is currently the most accurate diagnostic biomarker in GCF for periodontitis in systemically healthy patients [35]. In saliva, aMMP-8/MMP-8 is also among the best five biomarkers, and the combination of aMMP-8/MMP-8 and IL-6 seems the most promising salivary diagnostic marker for periodontitis [36,37].…”

“…Based on this evidence, therefore, we strongly support the call of Tonetti et al [1] for a paradigm shift to also consider periodontitis in terms of the inflammatory mediators that are immunoassay measures, offering information that traditionally used diagnostic methods are not able to provide as The utility of mouthrinse measurements is based on a simple technique to collect and sample gingival crevicular fluid (GCF) [14,21,53], instead of using more laborious filter papers or micropipettes [54]. Moreover, previous studies have also presented a better diagnostic accuracy value of GCF in aMMP-8 measurements in comparison to saliva when classifying periodontal health and disease [35][36][37]. However, it should also be noted that not all commercial kits detect active forms of MMP-8, as the aMMP-8 PoC mouthrinse test and IFMA used in this study do [29].…”

A Preliminary Study on the Ability of the Trypsin-Like Peptidase Activity Assay Kit to Detect Periodontitis

“…Additionally, metabolic profiling of saliva (combination of cadaverine, 5-oxoproline, and histidine) identified individuals, according to the CDC/AAP definition, with moderate/severe periodontitis with an AUC of 0.88 [40]. Moreover, a meta-analysis was recently performed for four biomarkers in GCF: MMP-8, elastase, cathepsin, and trypsin [41]. The median sensitivity and specificity were 77% and 92% for MMP-8, 75% and 81% for elastase, 73% and 67% for cathepsin, and 71% and 66% for trypsin, respectively.…”