Active matrix metalloproteinase-8 (aMMP-8) point-of-care test (POCT) in the COVID-19 pandemic

ABSTRACT

Introduction

Active matrix metalloproteinase (aMMP)-8 utilized in point-of-care testing (POCT) is regarded as a potential biomarker for periodontal and peri-implant diseases. Various host and microbial factors eventually influence the expression, degranulation, levels and activation of aMMP-8. The type of oral fluids (saliva, mouthrinse, gingival crevicular, and peri-implant sulcular fluids [GCF/PISF], respectively) affect the analysis.

Areas covered

With this background, we aimed to review here the recent studies on practical, inexpensive, noninvasive and quantitative mouthrinse and GCF/PISF chair-side POCT lateral flow aMMP-8 immunoassays (PerioSafe and ImplantSafe/ORALyzer) and how they help to detect, predict, monitor the course, treatment and prevention of periodontitis and peri-implantitis. The correlations of aMMP-8 POCT to other independent and catalytic activity assays of MMP-8 are also addressed.

Expert opinion

The mouthrinse aMMP-8 POCT can also detect prediabetes/diabetes and tissue destructive oral side-effects due to the head and neck cancers’ radiotherapy. Chlorhexidine and doxycycline can inhibit collagenolytic human neutrophil and GCF aMMP-8. Furthermore, by a set of case-series we demonstrate the potential of mouthrinse aMMP-8 POCT to real-time/online detect periodontitis as a potential risk disease for coronavirus disease 2019 (COVID-19). The clinical interdisciplinary utilization of aMMP-8 POCT requires additional oral, medical, and interdisciplinary studies.

KEYWORDS:

• Matrix metalloproteinase 8
• Covid-19
• oral fluids
• diagnostics
• mouth rinse
• biomarkers
• peri-implantitis
• periodontitis

Article highlights

• There is a need for reliable complementary adjunctive chair-side/point-of-care (POC) diagnostic tool in periodontitis and peri-implantitis. Lateral flow quantitative active matrix metalloproteinase (aMMP)-8 point-of-care testing (POCT) is a potential such tool with sensitivity 75–85% and specificity 80–90%. It agrees well with other independent catalytic protease activity assays of aMMP-8.

• aMMP-8 as the key biomarker can be implemented in the new periodontitis and peri-implantitis disease classification. Mouthrinse aMMP-8 POCT can additionally detect prediabetes/diabetes and tissue degenerative oral side-effects of head and neck cancer radiotherapy.

• Chlorhexidine and doxycycline can inhibit aMMP-8 originating from collagenolytic human neutrophils as well as from gingival crevicular fluid (GCF) of periodontitis patients

• Mouthrinse aMMP-8 POCT can furthermore be utilized to identify periodontitis as a potential risk disease for coronavirus disease 2019 (COVID-19).

• aMMP-8 -technology, as a systemic medical biomarker, is useful in cardiovascular diseases, diabetes, obesity, bacteremia, sepsis, meningitis, and pancreatitis.

Declaration of interest

Prof. Timo Sorsa is the inventor of U.S. 5,652,223, 5,736,341, 5,864,632, 6,143,476 and US 2017/0023571A1 (issued 6 June 2019), WO 2018/060553 A1 (issued 31 May 2018), 10,488,415 B2, and US 2017/0023671A1, Japanese Patent 2016-554,676 and South Korean patent 10-2016-7,025,378. Dr. Lorne M. Golub is listed as an inventor on several patents on host-modulation therapies and these have been fully assigned to his institution, Stony Brook University, State University of New York.

The other authors have no relevant affiliations or financial involvement with any organization or entity with a financial interest in or financial conflict with the subject matter or materials discussed in the manuscript. This includes employment, consultancies, honoraria, stock ownership or options, expert testimony, grants or patents received or pending, or royalties. The funders had no role in the design of the study; in the collection, analyses, or interpretation of data; in the writing of the manuscript, or in the decision to publish the results.

Reviewer disclosures

Peer reviewers on this manuscript have no relevant financial or other relationships to disclose

Additional information

Funding

This research was funded by the Helsinki and Uusimaa Hospital District (HUS) (TYH2016251,TYH2017251, TYH2018229, TYH2019319, Y1014SL017, Y1014SL018, Y1014SULE1), Finland; Suomen Hammaslääkäriseura Apollonia (Finnish Dental Association Apollonia), Finland; Karolinska Institutet, Sweden.