Browsing by Subject "saliva"

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  • Umeizudike, Kehinde Adesola; Lähteenmäki, Hanna; Räisänen, Ismo T.; Taylor, John J.; Preshaw, Philip M.; Bissett, Susan M.; Tervahartiala, Taina; O Nwhator, Solomon; Pärnänen, Pirjo; Sorsa, Timo (2022)
    Objective: The aim of this study was to determine the diagnostic utility of an MMP-8 biosensor assay in differentiating periodontal health from gingivitis and periodontitis and compare it with an established time-resolved immunofluorescence assay (IFMA) and enzyme-linked immunosorbent assay (ELISA). Background: Currently available antibody-based assays display a wide variability in their ability to accurately measure matrix metalloproteinase-8 (MMP-8) levels in saliva. Methods: Salivary MMP-8 levels were analyzed in 189 systemically healthy participants using an antibody-based biosensor prototype that operates using a surface acoustic wave technology and compared with IFMA and ELISA antibody assays. Participants were categorized into 3 groups: periodontal health (59), gingivitis (63), and periodontitis (67). A sub-population of participants (n = 20) with periodontitis received periodontal treatment and were monitored for 6 months. Results: All the assays demonstrated significantly higher salivary MMP-8 concentrations in participants with periodontitis versus gingivitis, periodontitis versus health, and gingivitis versus health (all p <.05). The biosensor data demonstrated significant correlations with IFMA (r =.354, p <.001) and ELISA (r =.681, p <.001). Significant reductions in salivary MMP-8 concentrations were detected by the biosensor (p =.030) and IFMA (p =.002) in participants with periodontitis 6 months after non-surgical periodontal treatment. IFMA had the best sensitivity (89.2%) for detecting periodontitis and gingivitis versus health and 96.6% for detecting periodontitis versus health and gingivitis. The biosensor had an AUC value of 0.81 and diagnostic accuracy of 74.2% for differentiating periodontitis and gingivitis from health; an AUC value of 0.86 and diagnostic accuracy of 82.8% for periodontitis versus health and gingivitis. Conclusions: The biosensor, IFMA, and ELISA assays differentiated between periodontal health, gingivitis, and periodontitis based on salivary MMP-8 levels. Only the biosensor and, particularly, IFMA identified an effect of periodontal treatment in the participants with periodontitis. Our findings support the potential utility of salivary oral fluid aMMP-8-based point-of-care technology in the future of periodontal diagnostics.
  • PAROKRANK Steering Comm; Rathnayake, Nilminie; Gustafsson, Anders; Sorsa, Timo; Norhammar, Anna; Bostanci, Nagihan (2022)
    Background: Peptidoglycan recognition protein 1 (PGLYRP1) is an antimicrobial and proinflammatory innate immunity protein activated during infections. We aimed to investigate whether PGYLRP1 and associated molecules of the immune response in saliva is a cumulative outcome result of both MI and periodontal inflammation. Methods and Results: Two hundred patients with MI and another 200 matched non-MI controls were included. A full-mouthexamination was conducted to assess periodontal inflammation and collection of stimulated saliva was performed 6 to 10 weeks after the first MI. PGLYRP1, triggering receptor expressed on myeloid cells 1 (TREM-1), interleukin-1 beta (IL-1 beta) were analyzed by ELISA. Matrix metalloproteinase (MMP)-8 levels were determined by IFMA. Compared to controls, MI patients showed higher salivary PGLYRP1, but not TRIM-1 levels. The difference in PGLYRP1 levels remained after adjustment for covariates. In MI patients, the PGLYRP1 levels positively correlated with BOP and PPD 4 to 5 mm. Among non-MI subjects, the levels of PGLYRP1 correlated positively and significantly with BOP and total PPD. Salivary PGLYRP1 concentrations also showed strong positive correlations with levels of TRIM-1, IL-1 beta and MM P-8. In multivariate linear regression analysis, in MI patients, BOP and former smokingstatus displayed an association with salivary PGLYRP1 concentration. Conclusion: MI patients showed higher salivary PGLYRP1 levels than healthy controls, also after adjusting for smoking, sex, age and periodontal health status. Salivary levels of PGLYRP1 may reflect the overall inflammatory burden to chronic bacterial exposure, possibly underpinning the observed associations between periodontitis and exposure with MI.
  • Paju, Susanna; Pietiäinen, Milla; Liljestrand, John; Lahdentausta, Laura; Salminen, Aino; Kallio, Elisa; Mäntylä, Päivi; Buhlin, Kåre; Hörkkö, Sohvi; Sinisalo, Juha; Pussinen, Pirkko (2021)
    Aim To study the prevalence of carotid artery calcification (CAC) in relation to apical and marginal periodontitis, subgingival dysbiotic bacterial species and serum and saliva immune responses against them. In addition, the aim was to analyse the association of CAC with angiographically verified coronary artery disease (CAD) and mortality. Methodology In the present random Parogene cohort, the patients had an indication for coronary angiography. Apical and marginal periodontitis were diagnosed during clinical and radiographic oral examinations, and CAC on panoramic radiographs (n = 492). Presence and severity of CAD were registered from angiography. Subgingival dysbiotic bacterial species were quantitated using checkerboard DNA-DNA-hybridization, and serum and saliva antibody levels were determined by immunoassays. The cohort was followed-up for 10 years or until death (median 9.9, range 0.21-10.4) via linkage to the national death register. The statistical models were adjusted for age, gender, smoking, hypertension, diabetes and dyslipidemia. Results A total of 102 (20.7%) patients had detectable CAC, which was moderate in 81 (16.4%) and severe in 21 (4.3%). CAC was associated (OR, 95% CI) with severe apical periodontitis (2.25, 1.15-4.41), root canal fillings (1.15, 1.04-1.26), alveolar bone loss (2.66, 1.21-5.84), severe periodontal inflammation (2.23, 1.11-4.47), high level of gram-negative subgingival species (2.73, 1.34-5.50), saliva IgG against dysbiotic species (1.05, 1.01-1.10/unit) and severe (2.58, 1.36-4.90) and chronic (2.13, 1.15-3.93) CAD. A total of 105 (20.7%) patients died during the follow-up and 53 (10.4%) deaths were because of cardiovascular diseases (CVD). Severe CAC predicted worse survival with HRs (95% CI) of 3.08 (1.58-6.06) for all-cause and 3.43 (1.42-8.25) for CVD death. Conclusions CAC on panoramic tomography was associated with (i) apical and marginal periodontitis and dysbiotic bacterial species giving rise to an immunological response, and with (ii) severe, chronic CAD and increased mortality. The results further emphasize the role of oral infections in CAD and the importance of referring a patient with CAC for a cardiovascular evaluation.
  • Salminen, Aino; Pietiäinen, Milla; Paju, Susanna; Sorsa, Timo; Mäntylä, Päivi; Buhlin, Kåre; Sinisalo, Juha; Pussinen, Pirkko J. (2022)
  • Gursoy, Ulvi Kahraman; Pussinen, Pirkko J.; Salomaa, Veikko; Syrjalainen, Sanna; Kononen, Eija (2018)
    Objective: Aim was to analyze the diagnostic ability of cumulative risk score (CRS), which uses salivary levels of Porphyromonas gingivalis, interleukin (IL)-1 beta, and matrix metalloproteinase (MMP)-8 in an adaptive design, compared to previously reported thresholds of each marker alone. Materials and Methods: Oral and general health information of 463 participants were included in the analysis. Having the percentage of bleeding on probing (BOP) > 25%, having at least two sites with probing pocket depth (PPD) of 4-5 mm or having at least one tooth with alveolar bone loss (ABL) of at least 1/3 of the root length were accepted as outcome variables. Being above the salivary threshold concentrations of P. gingivalis, IL-1 beta, and MMP-8 and CRS values were used as explanatory variables. Receiver operating characteristics (ROC) producing an area under the curve (AUC) and multinomial regression analysis were used in statistical analysis. Results: CRS provided AUCs larger than any other tested biomarker threshold. Sensitivity and specificity of CRS for detecting clinical markers of periodontitis were acceptable, and a strong association was observed between the highest CRS score and having at least two sites with PPD of 4-5 mm. Conclusion: CRS brings additional power over fixed thresholds of single biomarkers in detecting periodontitis.
  • Sali, Virpi; Veit, Christina; Valros, Anna; Junnikkala, Sami; Heinonen, Mari; Nordgreen, Janicke (2021)
    Infectious and inflammatory conditions are common especially in growing pigs. Lipopolysaccharide (LPS) is an important antigenic structure of Gram-negative bacteria and can be used to induce inflammation experimentally. As pigs are usually group-housed in commercial conditions, it is difficult to detect sick individuals, particularly at an early stage of illness. Acute phase proteins such as haptoglobin (Hp) are known indicators of an activated innate immune system whereas adenosine deaminase (ADA) is a relatively novel inflammatory biomarker in pigs. Both parameters can be measured in saliva and could be used as indicators of inflammation. Compared with blood sampling, saliva sampling is a less stressful procedure that is rapid, non-invasive and easy to perform both at group and at individual level. In this blinded randomized clinical trial, 32 female pigs at their post-weaning phase were allocated to one of four treatments comprising two injections of the following substance combinations: saline-saline (SS), ketoprofen-saline (KS), saline-LPS (SL), and ketoprofen-LPS (KL). First, ketoprofen or saline was administered intramuscularly on average 1 h before either LPS or saline was given through an ear vein catheter. In all groups, saliva was collected prior to injections (baseline) and at 4, 24, 48, and 72 h post-injection for determination of ADA, Hp, and cortisol concentrations. A multivariate model was applied to describe the dynamics of each biomarker. Pairwise relationships between ADA, Hp, and cortisol responses from baseline to 4 h post-injection within the SL group were studied with Spearman correlations. A significant increase in the SL group was seen in all biomarkers 4 h post-injection compared to baseline and other time points (pairwise comparisons, p < 0.01 for all) and ketoprofen alleviated the LPS effect. We found a significant positive correlation between ADA and Hp within the SL group (r = 0.86, p < 0.05). The primary and novel findings of the present study are the response of ADA to LPS, its time course and alleviation by ketoprofen. Our results support the evidence that ADA and Hp can be used as inflammatory biomarkers in pigs. We suggest further studies to be conducted in commercial settings with larger sample sizes.
  • Paju, Susanna; Tallgren, Marika; Kivimäki, Anne; Lahdentausta, Laura; Salminen, Aino; Oksanen, Lotta-Maria Adele Helena; Sanmark, Enni; Geneid, Ahmed; Pussinen, Pirkko; Pietiäinen, Milla (2022)
    Saliva is an alternative sample material to nasopharyngeal swab in SARS- CoV- 2 diagnostics. We investigated possible aspects to improve the reliability of SARS- CoV- 2 detection from saliva. Saliva was collected from asymptomatic healthy subjects (n=133) and COVID- 19 patients (n=9). SARS- CoV- 2 detection was performed with quantitative reverse- transcriptase PCR (RT- qPCR) with two viral and one host target serving as an internal control. The use of internal control revealed that in the first RT- qPCR run 25???30 % of assays failed. The failure is associated with poor RNA quality. When the amount of RNA was cut down to half from the original amount, the performance of RT- qPCR was greatly enhanced (95 % of the assays succeeded). The quality of RNA was not affected by the use of different nucleic acid stabilizing buffers. Our study showed that saliva is suitable material for RT- qPCR based SARS- CoV- 2 diagnostics, but the use of internal control is essential to distinguish the true negative samples from failed assays.
  • Sarfraz, Sonia; Mäntynen, Pilvi-Helinä; Laurila, Marisa; Suojanen, Juho; Saarnio, Juha; Rossi, Sami; Horelli, Jani; Kaakinen, Mika; Leikola, Junnu; Reunanen, Justus (2022)
    The aim of this study was to assess the biofilm formation of Streptococcus mutans, Staphylococcus aureus, Enterococcus faecalis, and Escherichia coli on titanium implants with CAD-CAM tooling techniques. Twenty specimens of titanium were studied: Titanium grade 2 tooled with a Planmeca CAD-CAM milling device (TiGrade 2), Ti6Al4V grade 5 as it comes from CAD-DMLS device (computer aided design-direct metal laser sintering device) (TiGrade 5), Ti6Al4V grade 23 as it comes from a CAD-CAM milling device (TiGrade 23), and CAD-DMLS TiGrade 5 polished with an abrasive disc (TiGrade 5 polished). Bacterial adhesion on the implants was completed with and without saliva treatment to mimic both extraoral and intraoral surgical methods of implant placement. Five specimens/implant types were used in the bacterial adhesion experiments. Autoclaved implant specimens were placed in petri plates and immersed in saliva solution for 30 min at room temperature and then washed 3x with 1x PBS. Bacterial suspensions of each strain were made and added to the specimens after saliva treatment. Biofilm was allowed to form for 24 h at 37 degrees C and the adhered bacteria was calculated. Tooling techniques had an insignificant effect on the bacterial adhesion by all the bacterial strains studied. However, there was a significant difference in biofilm formation between the saliva-treated and non-saliva-treated implants. Saliva contamination enhanced S. mutans, S. aureus, and E. faecalis adhesion in all material types studied. S. aureus was found to be the most adherent strain in the saliva-treated group, whereas E. coli was the most adherent strain in the non-saliva-treated group. In conclusion, CAD-CAM tooling techniques have little effect on bacterial adhesion. Saliva coating enhances the biofilm formation; therefore, saliva contamination of the implant must be minimized during implant placement. Further extensive studies are needed to evaluate the effects of surface treatments of the titanium implant on soft tissue response and to prevent the factors causing implant infection and failure.
  • Raju, Sajan C.; Lagström, Sonja; Ellonen, Pekka; de Vos, Willem M.; Eriksson, Johan G.; Weiderpass, Elisabete; Rounge, Trine B. (2019)
    Objective: The human intestinal microbiota likely play an important role in the development of overweight and obesity. However, the associations between saliva microbiota and body mass index (BMI) have been sparsely studied. The aim of this study was to identify the associations between saliva microbiota and body size in Finnish children. Methods: The saliva microbiota of 900 Finnish children, aged 11-14 years with measured height and weight, was characterized using 16S rRNA (V3-V4) sequencing. Results: The core saliva microbiota consisted of 14 genera that were present in more than 95% of the Finnish children. The saliva microbiota profiles were gender-specific with higher alpha-diversity in boys than girls and significant differences between the genders in community composition and abundances. Alpha-diversity differed between normal weight and overweight girls and between normal weight and obese boys. The composition was dissimilar between normal weight and obese girls, but not in boys. The relative abundance profiles differed according to body size. Decrease in commensal saliva bacteria were observed in all the body sizes when compared to normal weight children. Notably, the relative abundance of bacteria related to, Veillonella, Prevotella, Selenomonas, and Streptococcus was reduced in obese children. Conclusion: Saliva microbiota diversity and composition were significantly associated with body size and gender in Finnish children. Body size-specific saliva microbiota profiles open new avenues for studying the potential roles of microbiota in weight development and management.
  • Rounge, Trine B.; Page, Christian M.; Lepistö, Maija; Ellonen, Pekka; Andreassen, Bettina K.; Weiderpass, Elisabete (2016)
    Aim: We performed an epigenome-wide association study within the Finnish Health in Teens cohort to identify differential DNA methylation and its association with BMI in adolescents. Materials & methods: Differential DNA methylation analyses of 3.1 million CpG sites were performed in saliva samples from 50 lean and 50 heavy adolescent girls by genome-wide targeted bisulfite-sequencing. Results: We identified 100 CpG sites with p-values <0.000524, seven regions by 'bumphunting' and five CpG islands that differed significantly between the two groups. The ten CpG sites and regions most strongly associated with BMI substantially overlapped with obesity-and insulin-related genes, including MC2R, IGFBPL1, IP6K1 and IGF2BP1. Conclusion: Our findings suggest an association between the saliva methylome and BMI in adolescence.
  • Kannela, Niina (Helsingfors universitet, 2013)
    Cortisol is a vital hormone for normal bodily functions. Both physical and mental stress, as well as many diseases like the Cushing syndrome are known to increase the human cortisol levels. These levels can be measured in many biological matrixes, such as saliva. Traditionally, these measurements have been done by using immunoassays or liquid chromatographic-mass spectrometric methods (LC-MS). However, in the last few years, ambient ionization techniques, which are quick and easy to use, have also proven suitable for quantitative analysis of compounds in biological matrixes. Thus, these techniques could offer an alternative to traditional methods in the analysis of cortisol from human saliva. The aim of this study was to investigate the suitability of desorption atmospheric pressure photoionization (DAPPI) for quantitative analysis of steroids in saliva. The investigated steroids were dehydroepiandrosterone (DHEA), cortisol and testosterone. Because of the low quantities of testosterone and DHEA in saliva, the study was mainly focused on cortisol analysis. In this study, the ionization mechanism for the steroids was observed to be proton transfer with every tested spray solvent (acetone, chlorobentzene and toluene). Even though the choice of spray solvent did not change the ionization mechanism, it affected the efficiency of ionization. In cortisol measurements acetone was observed to be the best solvent. The temperature of the microchip, as well as the UV-lamp used (dc- or rf-lamp), only affected the ionization slightly. In this study, measuring cortisol in non-pretreated saliva was not successful. However, solid phase extraction (SPE) method for the pretreatment of saliva was optimized with high recovery for cortisol (106 %). The detection limit for cortisol (50 nM) in water samples and the linear area of cortisol in both water and pretreated saliva samples (500 nM - 10 µM) were also determined. Poor repeatability of DAPPI-system was the main challenge in these measurements. The DAPPI-MS-method developed in this study is suitable for analyzing cortisol in pretreated saliva samples. However, without further development it is not sensitive enough to be used in quantitative analysis of cortisol in salivary levels.
  • Herrala, Maria; Turunen, Soile; Hanhineva, Kati; Lehtonen, Marko; Mikkonen, Jopi J. W.; Seitsalo, Hubertus; Lappalainen, Reijo; Tjäderhane, Leo; Niemelä, Raija K.; Salo, Tuula; Myllymaa, Sami; Kullaa, Arja M.; Kärkkäinen, Olli (2021)
    Saliva is a complex oral fluid, and plays a major role in oral health. Primary Sjogren's syndrome (pSS), as an autoimmune disease that typically causes hyposalivation. In the present study, salivary metabolites were studied from stimulated saliva samples (n = 15) of female patients with pSS in a group treated with low-dose doxycycline (LDD), saliva samples (n = 10) of non-treated female patients with pSS, and saliva samples (n = 14) of healthy age-matched females as controls. Saliva samples were analyzed with liquid chromatography mass spectrometry (LC-MS) based on the non-targeted metabolomics method. The saliva metabolite profile differed between pSS patients and the healthy control (HC). In the pSS patients, the LDD treatment normalized saliva levels of several metabolites, including tyrosine glutamine dipeptide, phenylalanine isoleucine dipeptide, valine leucine dipeptide, phenylalanine, pantothenic acid (vitamin B5), urocanic acid, and salivary lipid cholesteryl palmitic acid (CE 16:0), to levels seen in the saliva samples of the HC. In conclusion, the data showed that pSS is associated with an altered saliva metabolite profile compared to the HC and that the LLD treatment normalized levels of several metabolites associated with dysbiosis of oral microbiota in pSS patients. The role of the saliva metabolome in pSS pathology needs to be further studied to clarify if saliva metabolite levels can be used to predict or monitor the progress and treatment of pSS.
  • Viljakainen, Jannina; Raju, Sajan C.; Viljakainen, Heli; Figueiredo, Rejane Augusta de Oliveira; Roos, Eva; Weiderpass, Elisabete; Rounge, Trine B. (2020)
    Background Diet may influence health directly or indirectly via the human microbiota, emphasizing the need to unravel these complex relationships for future health benefits. Associations between eating habits and gut microbiota have been shown, but less is known about the association between eating habits and saliva microbiota. Objective The aim of this study was to investigate if eating habits and meal patterns are associated with the saliva microbiota. Methods In total, 842 adolescents, aged 11-14 years, from the Finnish Health in Teens (Fin-HIT) study cohort were included in this study. Eating habits and breakfast and dinner patterns were derived from a web-based questionnaire answered in school. Three major eating habit groups were identified: fruit and vegetable avoiders (FV avoiders), healthy and unhealthy. Microbiota profiles were produced from 16S rRNA gene (V3-V4) sequencing of DNA from the saliva samples. Statistical models were adjusted for gender, age, parental language, body mass index (BMI) categories, and sequencing depth. Results Regular breakfast eaters had a higher alpha diversity (Shannon index with mean (standard error of means) 2.27 (0.03) vs. 2.22 (0.03), p = 0.06, inverse Simpson's index with 6.27 (0.17) vs. 5.80 (0.02), p = 0.01), and slight differences in bacterial composition (PERMANOVA: p = 0.001) compared with irregular breakfast eaters. A similar trend in alpha diversity was observed between regular and irregular dinner eaters (Shannon index with 2.27 (0.03) vs. 2.22 (0.03), p = 0.054, inverse Simpson's index with 6.23 (0.17) vs. 6.04 (0.22), p = 0.28), while no difference was found in composition (PERMANOVA: p = 0.08). No differences were identified between eating habit groups and saliva microbiota diversity (Shannon index p = 0.77, inverse Simpson's index p = 0.94) or composition (PERMANOVA: p = 0.13). FV avoiders, irregular breakfast eaters and irregular dinner eaters had high abundances of Prevotella. Conclusion Regularity of eating, especially breakfast eating, was associated with more diverse saliva microbiota and different composition compared with irregular eaters. However, the dissimilarities in composition were small between regular and irregular breakfast eaters. Our results suggest that Prevotella abundances in saliva were common in FV avoiders and meal skippers. However, the clinical implications of these findings need to be evaluated in future studies.
  • Gürsoy, Ulvi K.; Könönen, Eija; Tervahartiala, Taina; Gürsoy, Mervi; Pitkänen, Jari; Torvi, Paula; Suominen, Anna-Liisa; Pussinen, Pirkko; Sorsa, Timo (2018)
    Aim To investigate the molecular forms of salivary matrix metalloproteinase (MMP)-8 in relation to periodontitis. Materials and Methods Molecular forms, degree of activation and fragmentation of neutrophilic and mesenchymal-type MMP-8 isoforms were analysed from salivary samples of 81 subjects with generalized periodontitis, 63 subjects with localized periodontitis and 79 subjects without pocket teeth, by using western-immunoblots with computer quantitation. In addition, human recombinant proMMP-8 was in vitro activated by Treponema denticola chymotrypsin-like protease (Td-CTLP), sodium hypochlorite (NaOCl, 1 mM, oxidant) or amino phenyl mercuric acetate (APMA, 1 mM). Results In saliva of periodontitis-affected individuals, MMP-8 is found in multiple forms, that is, complexes, active and pro-forms of neutrophilic and mesenchymal-type MMP-8, and especially 20-27 kDa fragments. The quantity of these fragments was elevated in both localized and generalized forms of periodontitis. Moreover, the tested activators (Td-CTLP, NaOCl and APMA) activated inactive proMMP-8, resulting in fragments of 20-27 kDa, in vitro, and salivary concentrations of T. denticola correlated significantly with salivary levels of fragmented MMP-8. Conclusion The present results indicate that during the development and progression of periodontitis, MMP-8 appears as activated and fragmented, and treponemal proteases most likely play role in this cascade.
  • Lundmark, Anna; Johannsen, Gunnar; Eriksson, Kaja; Kats, Anna; Jansson, Leif; Tervahartiala, Taina; Rathnayake, Nilminie; Akerman, Sigvard; Klinge, Bjorn; Sorsa, Timo; Yucel-Lindberg, Tulay (2017)
    Aim: Periodontitis is a chronic inflammatory disease, characterized by irreversible destruction of tooth-supporting tissue including alveolar bone. We recently reported mucin 4 ( MUC4) and matrix metalloproteinase 7 (MMP7) as highly associated with periodontitis in gingival tissue biopsies. The aim of this study was to further investigate the levels of MUC4 and MMP7 in saliva and gingival crevicular fluid (GCF) samples of patients with periodontitis. Materials and Methods: Saliva and GCF samples were collected from periodontitis patients and healthy controls. The levels of MUC4, MMP7, and total protein concentrations were analysed using ELISA or Bradford assay. Results: MUC4 levels were significantly lower in saliva and GCF from periodontitis patients relative to healthy controls. MMP7 levels were significantly higher in saliva and GCF from periodontitis patients. Multivariate analysis revealed that MUC4 was significantly associated with periodontitis after adjusting for age and smoking habits and, moreover, that the combination of MUC4 and MMP7 accurately discriminated periodontitis from healthy controls. Conclusions: MUC4 and MMP7 may be utilized as possible novel biomarkers for periodontitis.
  • Pietiäinen, Milla; Liljestrand, John M.; Akhi, Ramin; Buhlin, Kåre; Johansson, Anders; Paju, Susanna; Salminen, Aino; Mäntylä, Päivi; Sinisalo, Juha; Tjäderhane, Leo; Hörkkö, Sohvi; Pussinen, Pirkko (2019)
    Apical periodontitis is an inflammatory reaction at the apex of an infected tooth. Its microbiota resembles that of marginal periodontitis and may induce local and systemic antibodies binding to bacteria- and host-derived epitopes. Our aim was to investigate the features of the adaptive immune response in apical periodontitis. The present Parogene cohort (n = 453) comprises patients with cardiac symptoms. Clinical and radiographic oral examination was performed to diagnose apical and marginal periodontitis. A three-category endodontic lesion score was designed. Antibodies binding to the bacteria- and host-derived epitopes were determined from saliva and serum, and bacterial compositions were examined from saliva and subgingival samples. The significant ORs (95% CI) for the highest endodontic scores were observed for saliva IgA and IgG to bacterial antigens (2.90 (1.01-8.33) and 4.91 (2.48-9.71)/log10 unit), saliva cross-reacting IgG (2.10 (1.48-2.97)), serum IgG to bacterial antigens (4.66 (1.22-10.1)), and Gram-negative subgingival species (1.98 (1.16-3.37)). In a subgroup without marginal periodontitis, only saliva IgG against bacterial antigens associated with untreated apical periodontitis (4.77 (1.05-21.7)). Apical periodontitis associates with versatile adaptive immune responses against both bacterial- and host-derived epitopes independently of marginal periodontitis. Saliva immunoglobulins could be useful biomarkers of oral infections including apical periodontitis-a putative risk factor for systemic diseases.
  • Norrman, Annika E; Tervahartiala, Taina; Sahlberg, Ella; Sorsa, Timo; Ruokonen, Hellevi; Grönroos, Lisa; Meurman, Jukka; Isoniemi, Helena; Nordin, Arno; Åberg, Fredrik; Helenius-Hietala, Jaana (2021)
    Salivary biomarkers have been linked to various systemic diseases. We examined the association between salivary biomarkers, periodontal health, and microbial burden in liver transplant (LT) recipients with and without diabetes, after transplantation. We hypothesized that diabetic recipients would exhibit impaired parameters. This study included 84 adults who received an LT between 2000 and 2006 in Finland. Dental treatment preceded transplantation. The recipients were re-examined, on average, six years later. We evaluated a battery of salivary biomarkers, microbiota, and subjective oral symptoms. Periodontal health was assessed, and immunosuppressive treatments were recorded. Recipients with impaired periodontal health showed higher matrix metalloproteinase-8 (MMP-8) levels (p < 0.05) and MMP-8/tissue inhibitor of matrix metalloproteinase 1 (TIMP1) ratios (p < 0.001) than recipients with good periodontal health. Diabetes post-LT was associated with impaired periodontal health (p < 0.05). No difference between groups was found in the microbial counts. Salivary biomarker levels did not seem to be affected by diabetes. However, the advanced pro-inflammatory state induced by and associated with periodontal inflammation was reflected in the salivary biomarker levels, especially MMP-8 and the MMP-8/TIMP-1 molar ratio. Thus, these salivary biomarkers may be useful for monitoring the oral inflammatory state and the course of LT recipients.
  • Keles Yucel, Zeynep Pinar; Silbereisen, Angelika; Emingil, Gulnur; Tokgoz, Yavuz; Kose, Timur; Sorsa, Timo; Tsilingaridis, Georgios; Bostanci, Nagihan (2020)
    Abstract Background Cystic fibrosis (CF) is a life-threatening chronic inflammatory disease in children due to respiratory complications. Saliva could serve as reservoir of bacterial colonization and potentially reflect systemic inflammation. This study investigated whether salivary triggering receptor expressed on myeloid cells 1 (TREM-1), peptidoglycan recognition protein 1 (PGLYRP1), interleukin (IL)-1? and calprotectin are associated with CF or reflect concomitant gingival inflammation. Methods Ten CF (age:3-12yrs) and ten systemically healthy age-and-gender-matched children (C) were enrolled in the study. Individuals with CF underwent routine laboratory determinations. Probing pocket depth (PPD), gingival index (GI), plaque index (PI) and bleeding on probing (BOP) were recorded on fully erupted teeth and saliva samples collected. Salivary TREM-1, PGLYRP1, IL-1? and calprotectin were analysed by ELISA. Results Children with CF had significantly higher BOP scores (P = 0.001) and calprotectin levels (P = 0.017) compared to the C group. TREM-1, PGLYRP1 and IL-1? could not distinguish between CF and SH but showed positive correlation with GI, PI and BOP in both groups. Calprotectin levels positively correlated with procalcitonin (P = 0.014), thrombocyte counts (P = 0.001), mean platelet volume (P = 0.030) and with PGLYRP1 (P = 0.019) and IL-1? (P = 0.013) in CF children. Receiver operating characteristic curve analysis for calprotectin (CFvsC) showed an area under the curve of 0.79 (95% CI 0.58-0.99, P = 0.034). Conclusions CF children presented with higher gingival inflammation scores and salivary calprotectin levels, that correlated with systemic inflammatory markers. Salivary calprotectin levels were not associated with periodontal parameters. Hence, preliminary data demonstrate that salivary calprotectin might have a chairside diagnostic potential for CF in children. This article is protected by copyright. All rights reserved
  • Føske Johnsen, Julie; Chincarini, Matteo; Sogstad, Åse Margrethe; Sølverød, Liv; Vatne, Marie; Mejdell, Cecilie Marie; Hänninen, Laura Talvikki (2019)
    The diagnosis of inadequate transfer of colostrum Immunoglobulin G (IgG) to calf serum, often known as failure of passive transfer (< 10 g/L IgG1 at 24-48 h), necessitates blood sampling from the calf and in some instances the presence of a veterinarian. Sampling saliva is both less invasive and easy for the producer. Previous research has shown that quantification of saliva IgG is possible in juvenile and adult cattle. The objectives of this observational pilot study were to investigate whether IgG can be quantified in neonatal calf saliva, if it is correlated to serum IgG concentrations, and if the indirect quantification of saliva IgG is achievable by use of a digital refractometer. Paired blood and saliva samples were collected from 20 healthy dairy calves aged 1-3 d. In these samples, IgG was quantified directly with Single Radial Immunodiffusion (SRID) and indirectly by use of a digital refractometer indicating Brix % (a subsample of n=12 saliva samples). A strong positive correlation (r = 0.7, P<0.001) between saliva IgG (mean ± SD; 0.2 ± 0.11 g/L) and serum IgG (32.1 ± 11.94 g/L) was found. Saliva IgG ranged from the lowest detectable value, 0.1 g/L (n = 6 samples), to 0.6 g/L. Saliva Brix (1.2 ± 0.69%) was not significantly correlated to serum IgG (n = 12, r = 0.43, P = 0.155), however it was significantly correlated to saliva IgG (n = 12, r = 0.7, P = 0.018) and Brix in serum (n = 12, r = 0.7, P = 0.013). We conclude that IgG was quantifiable in most of the saliva samples. For saliva IgG to be of any value with regards to detecting failure of passive transfer, future studies should investigate methods that can detect IgG <0.1 g/L. The results indicate that saliva IgG can be used to predict serum IgG at levels above 10g/L, which may warrant further exploration of the use of saliva in the surveillance of failure of passive transfer. The results of the current pilot study did not support the potential usage of a Brix % refractometer to quantify saliva IgG.
  • Kopra, Elisa; Lahdentausta, Laura; Pietiäinen, Milla; Buhlin, Kåre; Mäntylä, Päivi; Hörkkö, Sohvi; Persson, Rutger; Paju, Susanna; Sinisalo, Juha; Salminen, Aino; Pussinen, Pirkko J. (2021)
    The use of systemic antibiotics may influence the oral microbiota composition. Our aim was to investigate in this retrospective study whether the use of prescribed antibiotics associate with periodontal status, oral microbiota, and antibodies against the periodontal pathogens. The Social Insurance Institution of Finland Data provided the data on the use of systemic antibiotics by record linkage to purchased medications and entitled reimbursements up to 1 year before the oral examination and sampling. Six different classes of antibiotics were considered. The Parogene cohort included 505 subjects undergoing coronary angiography with the mean (SD) age of 63.4 (9.2) years and 65% of males. Subgingival plaque samples were analysed using the checkerboard DNA-DNA hybridisation. Serum and saliva antibody levels to periodontal pathogens were analysed with immunoassays and lipopolysaccharide (LPS) activity with the LAL assay. Systemic antibiotics were prescribed for 261 (51.7%) patients during the preceding year. The mean number of prescriptions among them was 2.13 (range 1-12), and 29.4% of the prescriptions were cephalosporins, 25.7% penicillins, 14.3% quinolones, 12.7% macrolides or lincomycin, 12.0% tetracycline, and 5.8% trimethoprim or sulphonamides. In linear regression models adjusted for age, sex, current smoking, and diabetes, number of antibiotic courses associated significantly with low periodontal inflammation burden index (PIBI, p < 0.001), bleeding on probing (BOP, p = 0.006), and alveolar bone loss (ABL, p = 0.042). Cephalosporins associated with all the parameters. The phyla mainly affected by the antibiotics were Bacteroidetes and Spirochaetes. Their levels were inversely associated with the number of prescriptions (p = 0.010 and p < 0.001) and directly associated with the time since the last prescription (p = 0.019 and p < 0.001). Significant inverse associations were observed between the number of prescriptions and saliva concentrations of Prevotella intermedia, Tannerella forsythia, and Treponema denticola and subgingival bacterial amounts of Porphyromonas gingivalis, P. intermedia, T. forsythia, and T. denticola. Saliva or serum antibody levels did not present an association with the use of antibiotics. Both serum (p = 0.031) and saliva (p = 0.032) LPS activity was lower in patients having any antibiotic course less than 1 month before sampling. Systemic antibiotics have effects on periodontal inflammation and oral microbiota composition, whereas the effects on host immune responses against the periodontal biomarker species seem unchanged.