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    A comparative analysis of treatment-related changes in the diagnostic biomarker active metalloproteinase-8 levels in patients with periodontitis
    (2023) Keskin, Mutlu; Rintamarttunen, Juulia; Gülçiçek, Emre; Räisänen, Ismo T.; Gupta, Shipra; Tervahartiala, Taina; Pätilä, Tommi; Sorsa, Timo
    Background: Previous studies have revealed the potential diagnostic utility of aMMP-8, an active form of MMP-8, in periodontal and peri-implant diseases. While non-invasive point-of-care (PoC) chairside aMMP-8 tests have shown promise in this regard, there is a dearth of literature on the evaluation of treatment response using these tests. The present study aimed to investigate treatment-related changes in aMMP-8 levels in individuals with Stage III/IV-Grade C periodontitis compared to a healthy control group, using a quantitative chairside PoC aMMP-8 test, and to determine its correlation with clinical parameters. Methods: The study included 27 adult patients (13 smoker, 14 non-smoker) with stage III/IV-grade C periodontitis and 25 healthy adult subjects. Clinical periodontal measurements, real-time PoC aMMP-8, IFMA aMMP-8, and Western immunoblot analyses were performed before and 1 month after anti-infective scaling and root planing periodontal treatment. Time 0 measurements were taken from the healthy control group to test the consistency of the diagnostic test. Results: Both PoC aMMP-8 and IFMA aMMP-8 tests showed a statistically significant decrease in aMMP-8 levels and improvement in periodontal clinical parameters following treatment (p < 0.05). The PoC aMMP-8 test had high diagnostic sensitivity (85.2%) and specificity (100.0%) for periodontitis and was not affected by smoking (p > 0.05). Treatment also reduced MMP-8 immunoreactivity and activation as demonstrated by Western immunoblot analysis. Conclusion: The PoC aMMP-8 test shows promise as a useful tool for the real-time diagnosis and monitoring of periodontal therapy.
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    aMMP-8 oral Fluid PoC test in relation to oral and systemic diseases
    (2022) Sorsa, Timo; Nwhator, Solomon Olusegun; Sakellari, Dimitra; Grigoriadis, Andreas; Umeizudike, Kehinde Adesola; Brandt, Ella; Keskin, Mutlu; Tervahartiala, Taina; Parnanen, Pirjo; Gupta, Shipra; Mohindra, Ritin; Bostancı, Nagihan; Buduneli, Nurcan; Raisanen, Ismo Tapani
    The manuscript uses the previously published literature and highlights the benefits of active-matrix metalloproteinase (aMMP)-8 chairside/point-of-care (PoC) diagnostic tools as adjunctive measures in oral and systemic diseases. Previous studies suggest that as a biomarker, aMMP-8 is more precise than total MMP-8, MMP-9, MMP-2, MMP-3, MMP-13, MMP-7, MMP-1, calprotectin, myeloperoxidase (MPO), human neutrophil elastase (HNE), tissue inhibitor of matrix metalloproteinase (TIMP)-1, and bleeding of probing (BOP). Therefore, aMMP-8 could be implemented as the needed key biomarker for the new disease classification for both periodontitis and peri-implantitis. With a sensitivity to the tune of 75-85% and specificity in the range of 80-90%, lateral flow aMMP-8 PoC testing is comparable to catalytic protease activity assays for aMMP-8. The test can be further applied to estimate the glycemic status of an individual, to ascertain whether a person is at risk for COVID-19, in managing the oral side effects of radiotherapy carried in head and neck cancers, and in selected cases pertaining to reproductive health. In the future, aMMP-8 could find application as a potential systemic biomarker in diseases affecting the cardiovascular system, cancers, bacteremia, sepsis, diabetes, obesity, meningitis, as well as pancreatitis. The aMMP-8 PoCT is the first practical test in the emerging new dental clinical field, that is, oral clinical chemistry representing oral medicine, clinical chemistry, peri-implantology, and periodontology.
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    Author Response: Radiotherapy Increases aMMP-8-Levels and Neutrophil/Lymphocyte Ratio Rapidly in Head and Neck Cancer Patients: A Pilot Study
    (2023) Brandt, Ella; Keskin, Mutlu; Tervahartiala, Taina; Yılmaz, Mustafa; Harmankaya, İlknur; Karaçetin, Didem; İpek, Turgut; Gürsoy, Ulvi Kahraman; Rautava, Jaana; Gupta, Shipra; Hagström, Jaana; Raisanen, Ismo T.; Sorsa, Timo
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    Periodontal disease - a late complication of head and neck cancer radiotherapy
    (2024) Brandt, Ella; Keskin, Mutlu; Raisanen, Ismo T.; Makitie, Antti; Patila, Tommi; Sorsa, Timo; Gupta, Shipra
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    Radiotherapy increases aMMP-8-levels and neutrophil/lymphocyte ratio rapidly in head and neck cancer patients: a pilot study
    (2023) Brandt, Ella; Keskin, Mutlu; Tervahartiala, Taina; Yılmaz, Mustafa; Harmankaya, İlknur; Karaçetin, Didem; İpek, Turgut; Gürsoy, Ulvi Kahraman; Rautava, Jaana; Gupta, Shipra; Hagström, Jaana; Raisanen, Ismo T.; Sorsa, Timo
    Radiotherapy for head and neck carcinoma (HNC) has both curative and palliative purposes. This study investigated mouthrinse aMMP-8 levels, molecular forms of MMP-8, blood neutrophil counts and neurophil/lymphocyte ratios before and 3 weeks after HNC radiotherapy started. Thirteen HNC patients undergoing radiotherapy were included. Mouthrinse samples (before and 3 weeks after HNC radiotherapy had started) were assayed quantitatively by aMMP-8 point-of-care-kit (PerioSafe®/ORALyzer®) and by western immunoblot. Total neutrophil counts and neutrophil/lymphocyte ratios were evaluated in the hemogram results. Three weeks after HNC radiotherapy started, significant increases in aMMP-8 levels and neutrophil/lymphocyte ratios were observed. No significant difference was found in total neutrophil counts. Elevations of the activated and fragmented MMP-8 levels after HNC radiotherapy application were observed on western immunoblot analysis. The increase in the aMMP-8 levels and neutrophil/lymphocyte ratios indicate inflammation both locally and systemically suggesting increased risk for periodontitis due to the HNC radiotherapy.