The Ability of Quantitative, Specific, and Sensitive Point-of-Care/Chair-Side Oral Fluid Immunotests for aMMP-8 to Detect Periodontal and Peri-Implant Diseases

Saeed Alassiri, Pirjo Parnanen, Nilminie Rathnayake, Gunnar Johannsen, Anna-Maria Heikkinen, Richard Lazzara, Peter van der Schoor, Jan Gerrit van der Schoor, Taina Tervahartiala, Dirk Gieselmann, Timo Sorsa, Saeed Alassiri, Pirjo Parnanen, Nilminie Rathnayake, Gunnar Johannsen, Anna-Maria Heikkinen, Richard Lazzara, Peter van der Schoor, Jan Gerrit van der Schoor, Taina Tervahartiala, Dirk Gieselmann, Timo Sorsa

Abstract

The analysis of the disease-specific oral and systemic biomarkers in saliva and oral fluids (i.e., mouth rinse, gingival crevicular fluid (GCF), and peri-implantitis fluid (PISF)) is demanding. Several hosts and microbial factors may influence their expression, release, and levels. The type of saliva/oral fluids utilized for the diagnostics affects the analysis. High sensitivity and specificities together with sophisticated methods and techniques are essential for valuable outcome. We describe here recently developed practical, convenient, inexpensive, noninvasive, and quantitative mouth rinse and PISF/GCF/chair-side/point-of-care (PoC) lateral-flow aMMP-8 immunoassays (PerioSafe and ImplantSafe/ORALyser) to detect, predict, and monitor successfully the course, treatment, and prevention of periodontitis and peri-implantitis, respectively. The tests have been independently and successfully validated to differentiate periodontal and peri-implant health and disease in Finland, Germany, Netherland, Sweden, Turkey, Nigeria, Malawi, and USA. The clinical use of salivary/oral fluid biomarkers to identify oral and systemic conditions requires additional studies utilizing these noninvasive screening, diagnostic, and preventive aMMP-8 PoC/chair-side technologies.

Figures

Figure 1
Figure 1
aMMP-8 chair-side levels analysed visually (+/−) and quantitated for aMMP-8 (ng/ml) by ORALyser reader to monitor the effect of periodontal treatment (scaling and root planing) on chronic periodontitis (n = 10) (a) and healthy controls (n = 10) (b).
Figure 2
Figure 2
Peri-implant sulcular fluid (PISF) collected from 29 peri-implantitis and 32 periodontally healthy sites were tested for elevated aMMP-8 by ImplantSafe PoC/chair-side test (+/−), analysed for aMMP-8 (ng/ml) by immunofluorometric assay (IFMA), and by quantitated gelatin zymography for all molecular weight forms of gelatinase-B (MMP-9, zymographic densitometric units) (a). Implantitis sites were tested before and after surgical treatment by ImplantSafe (+/−); treatment caused positive sites to be negative (b). Elevated aMMP-8 levels in PISF detected by ImplantSafe positivity and IFMA associated significantly with peri-implantitis (p < 0.0001, Wilcoxon test (∗∗∗)) and could thus be conveniently PoC detected in 5 min by ImplantSafe. Any forms or total MMP-9 did –not differentiate peri-implantitis and healthy sites (a).

References

    1. Kinane D. F., Stathopoulou P. G., Papapanou P. N. Periodontal diseases. Nature Reviews Disease Primers. 2017;3, article 17038 doi: 10.1038/nrdp.2017.38.
    1. Lang N. P., Joss A., Orsanic T., Gusberti F. A., Siegrist B. E. Bleeding on probing. A predictor for the progression of periodontal disease? Journal of Clinical Periodontology. 1986;13(6):590–596. doi: 10.1111/j.1600-051x.1986.tb00852.x.
    1. Herr A. E., Hatch A. V., Throckmorton D. J., et al. Microfluidic immunoassays as rapid saliva-based clinical diagnostics. Proceedings of the National Academy of Sciences of the United States of America. 2007;104(13):5268–5273. doi: 10.1073/pnas.0607254104.
    1. Sorsa T., Gieselmann D., Arweiler N. B., Hernández M. A quantitative point-of-care test for periodontal and dental peri-implant diseases. Nature Reviews Disease Primers. 2017;3, article 17069 doi: 10.1038/nrdp.2017.69.
    1. Sorsa T., Heikkinen A. M., Leppilahti J., et al. Active matrix metalloproteinase-8: contributor to periodontitis and a missing link between genetics, dentistry, and medicine. In: Bostanci N., Belibasakis G. N., editors. Pathogenesis of Periodontal Diseases. Cham: Springer International Publishing; 2018. pp. 51–57.
    1. de Morais E. F., Pinheiro J. C., Leite R. B., Santos P. P. A., Barboza C. A. G., Freitas R. A. Matrix metalloproteinase-8 levels in periodontal disease patients: a systematic review. Journal of Periodontal Research. 2018;53(2):156–163. doi: 10.1111/jre.12495.
    1. de de Morais E. F., Dantas A. N., Pinheiro J. C., et al. Matrix metalloproteinase-8 analysis in patients with periodontal disease with prediabetes or type 2 diabetes mellitus: a systematic review. Archives of Oral Biology. 2018;87:43–51. doi: 10.1016/j.archoralbio.2017.12.008.
    1. Lee W., Aitken S., Sodek J., McCulloch C. A. G. Evidence of a direct relationship between neutrophil collagenase activity and periodontal tissue destruction in vivo: role of active enzyme in human periodontitis. Journal of Periodontal Research. 1995;30(1):23–33. doi: 10.1111/j.1600-0765.1995.tb01249.x.
    1. Mancini S., Romanelli R., Laschinger C. A., Overall C. M., Sodek J., McCulloch C. A. G. Assessment of a novel screening test for neutrophil collagenase activity in the diagnosis of periodontal diseases. Journal of Periodontology. 1999;70(11):1292–1302. doi: 10.1902/jop.1999.70.11.1292.
    1. Romanelli R., Mancini S., Laschinger C., Overall C. M., Sodek J., McCulloch C. Activation of neutrophil collagenase in periodontitis. Infection and Immunity. 1999;67(5):2319–2326.
    1. Leppilahti J. M., Kallio M. A., Tervahartiala T., Sorsa T., Mäntylä P. Gingival crevicular fluid matrix metalloproteinase-8 levels predict treatment outcome among smokers with chronic periodontitis. Journal of Periodontology. 2014;85(2):250–260. doi: 10.1902/jop.2013.130156.
    1. Axelsson P., Nyström B., Lindhe J. The long-term effect of a plaque control program on tooth mortality, caries and periodontal disease in adults. Results after 30 years of maintenance. Journal of Clinical Periodontology. 2004;31(9):749–757. doi: 10.1111/j.1600-051X.2004.00563.x.
    1. Ziebolz D., Schmalz G., Gollasch D., Eickholz P., Rinke S. Microbiological and aMMP-8 findings depending on peri-implant disease in patients undergoing supportive implant therapy. Diagnostic Microbiology and Infectious Disease. 2017;88(1):47–52. doi: 10.1016/j.diagmicrobio.2017.02.008.
    1. Nwhator S. O., Ayanbadejo P. O., Umeizudike K. A., et al. Clinical correlates of a lateral-flow immunoassay oral risk indicator. Journal of Periodontology. 2014;85(1):188–194. doi: 10.1902/jop.2013.130116.
    1. Mäntylä P., Stenman M., Kinane D. F., et al. Gingival crevicular fluid collagenase-2 (MMP-8) test stick for chair-side monitoring of periodontitis. Journal of Periodontal Research. 2003;38(4):436–439. doi: 10.1034/j.1600-0765.2003.00677.x.
    1. Shochet T., Comstock I. A., Ngoc N. T. N., et al. Results of a pilot study in the U.S. and Vietnam to assess the utility and acceptability of a multi-level pregnancy test (MLPT) for home monitoring of hCG trends after assisted reproduction. BMC Women's Health. 2017;17(1):p. 67. doi: 10.1186/s12905-017-0422-y.
    1. Prazuck T., Karon S., Gubavu C., et al. A finger-stick whole-blood HIV self-test as an HIV screening tool adapted to the general public. PLoS ONE. 2016;11(2, article e0146755) doi: 10.1371/journal.pone.0146755.
    1. Mombelli A., Lang N. P. The diagnosis and treatment of peri-implantitis. Periodontology 2000. 1998;17(1):63–76. doi: 10.1111/j.1600-0757.1998.tb00124.x.
    1. .
    1. Sorsa T., Salo T., Koivunen E., et al. Activation of type IV procollagenases by human tumor-associated trypsin-2. Journal of Biological Chemistry. 1997;272(34):21067–21074. doi: 10.1074/jbc.272.34.21067.
    1. Heikkinen A. M., Raivisto T., Kettunen K., et al. Pilot study on the genetic background of an active matrix metalloproteinase-8 test in Finnish adolescents. Journal of Periodontology. 2017;88(5):464–472. doi: 10.1902/jop.2016.160441.
    1. Izadi Borujeni S., Mayer M., Eickholz P. Activated matrix metalloproteinase-8 in saliva as diagnostic test for periodontal disease? A case-control study. Medical Microbiology and Immunology. 2015;204(6):665–672. doi: 10.1007/s00430-015-0413-2.
    1. Lorenz K., Keller T., Noack B., Freitag A., Netuschil L., Hoffmann T. Evaluation of a novel point-of-care test for active matrix metalloproteinase-8: agreement between qualitative and quantitative measurements and relation to periodontal inflammation. Journal of Periodontal Research. 2017;52(2):277–284. doi: 10.1111/jre.12392.
    1. Johnson N., Ebersole J. L., Kryscio R. J., et al. Rapid assessment of salivary MMP-8 and periodontal disease using lateral flow immunoassay. Oral Diseases. 2016;22(7):681–687. doi: 10.1111/odi.12521.
    1. Ritzer J., Lühmann T., Rode C., et al. Diagnosing peri-implant disease using the tongue as a 24/7 detector. Nature Communications. 2017;8(1):264–272. doi: 10.1038/s41467-017-00340-x.
    1. Nieminen M. T., Listyarifah D., Hagström J., et al. Treponema denticola chymotrypsin-like proteinase may contribute to orodigestive carcinogenesis through immunomodulation. British Journal of Cancer. 2017;118(3):428–434. doi: 10.1038/bjc.2017.409.
    1. Pärnänen P., Meurman J. H., Sorsa T. The effects of Candida proteinases on human proMMP-9, TIMP-1 and TIMP-2. Mycoses. 2011;54(4):325–330. doi: 10.1111/j.1439-0507.2010.01889.x.
    1. O’Brien-Simpson N. M., Burgess K., Lenzo J. C., Brammar G. C., Darby I. B., Reynolds E. C. Rapid chair-side test for detection of Porphyromonas gingivalis. Journal of Dental Research. 2017;96(6):618–625. doi: 10.1177/0022034517691720.
    1. Kido J.-I., Murakami S., Kitamura M., et al. Useful immunochromatographic assay of calprotectin in gingival crevicular fluid for diagnosis of diseased sites in patients with periodontal diseases. Journal of Periodontology. 2017;89(1):67–75. doi: 10.1902/jop.2017.170206.
    1. Myntti T., Rahkonen L., Nupponen I., et al. Amniotic fluid infection in preterm pregnancies with intact membranes. Disease Markers. 2017;2017:9. doi: 10.1155/2017/8167276.8167276
    1. Nieminen M. T., Vesterinen P., Tervahartiala T., et al. Practical implications of novel serum ELISA-assay for matrix metalloproteinase-8 in acute cardiac diagnostics. Acute Cardiac Care. 2015;17(3):46–47. doi: 10.3109/17482941.2015.1115077.

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