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Reference | Analysis | Markers | Aim | Main findings |
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[36] | Enzyme assay (fluorimetric MMP kit) | MMP-1, -2, -3, -8, -9, -12, -13 | To measure the levels of MMP in children with and without aggressive periodontitis (AgP). | The levels of MMP were raised in AgP sites compared to nondiseased sites in the same subjects. |
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[37] | ELISA | Myeloid related protein (MRP) 8/14, MRP14, total protein | To determine if the total protein, MRP14, and MRP8/14 in GCF can differentiate healthy from periodontitis sites in CP patients and if they could differentiate healthy subjects from CP patients. | These markers could not differentiate healthy from periodontitis sites in CP patients, but their levels in CP patients were higher than in healthy subjects. |
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[38] | Bradford method | Protein carbonyl (PC) | To assess GCF and serum levels of PC in patients with CP. | There was an increase in PC levels among CP patients, more than in healthy subjects. |
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[39] | ELISA, automatic colorimetric method | Total oxidant status (TOS), RANK ligand (RANKL), osteoprotegerin (OPG) | To explore the levels of total oxidant status (TOS), OPG, and RANKL levels in GCF and serum in different periodontal disease stages. | TOS, OPG, and RANKL levels increased with the severity of periodontal disease. |
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[40] | ELISA | Calprotectin, osteocalcin, cross-linked N-terminal telopeptide (NTx) | To evaluate the levels of osteocalcin, NTx, and calprotectin in GCF among healthy, G, CP, and generalized aggressive periodontitis (GAgP) patients. | Calprotectin level in GCF was considered as a marker for periodontal disease, while osteocalcin and NTx levels could indicate abnormal bone turnover. |
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[41] | ELISA | IL-1β, IL-6, IL-11, OSM, leukemia inhibitory factor (LIF) | To determine the concentrations of IL-1β, IL-11, IL-6, OSM, and LIF in GCF and plasma among periodontally diseased patients. | IL-1β, IL-11, and IL-6 GCF levels increased, but not plasma levels. They were considered dependable inflammatory biomarkers in periodontal diseases. |
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[42] | ELISA | Soluble triggering receptor expressed on myeloid cells 1 (sTREM-1) | To evaluate sTREM-1 levels in GCF of subjects with and without GAgP or CP and their association with subgingival plaque bacteria. | Elevated sTREM-1 levels at diseased sites and their positive association with clinical and microbiologic parameters strengthen the correlation of this marker with periodontitis. |
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[43] | ELISA, quantitative time-resolved immunofluorometric assay (IFMA) | MMP-8, MMP-13, tissue inhibitor of matrix metalloproteinase- (TIMP-) 1 | To compare GCF levels of MMP-13 and -8 and TIMP-1 in periodontitis patients with and without RA. | RA did not affect the clinical periodontal parameters. |
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[44] | ELISA | RANKL, OPG | To determine the level of OPG and RANKL in GCF after nonsurgical periodontal treatment. | It could be a good indicator of treatment success. |
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[45] | ELISA | IL-33 | To determine if IL-33 levels in GCF, saliva, and plasma could be used to differentiate between healthy and CP patients. | IL-33 levels could not be used as a biomarker for periodontal disease. |
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[46] | Electrochemiluminescence technique | Osteocalcin | To measure saliva, plasma, and GCF osteocalcin levels and correlate them with osteoporosis and periodontitis. | GCF osteocalcin levels were associated with periodontal disease only. |
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[47] | ELISA, multiplexed bead immunoassay (MPBI), SPM | IL-1β, -18, elastase, MMP-8, -9 | To evaluate the effect of scaling and root planning on periodontal status and on the levels of IL-1β, elastase, MMP-9, and MMP-8 in patients with and without T2DM. | Scaling and root planning reduced the levels of IL-1β, elastase, MMP-9, and MMP-8 in both groups. |
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[48] | ELISA | TNFα, RANKL | To measure the TNFα and RANKL concentrations in GCF of patients with AgP, after photodynamic or nonsurgical periodontal treatment. | Both types of treatment had the same influence on TNF-α and RANKL concentrations. |
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[49] | MPBI | IL-6, -4, -10, -13, -17, TNFα, macrophage inflammatory protein- (MIP-) 1α, MIP-1β, MCP1, regulated on activation normal T-cell expressed and secreted (RANTES) | To determine the effect of adjunctive sub-antimicrobial-dose doxycycline (SDD) on the local inflammatory response through chemokine and cytokine levels in GCF samples from CP patients. | SDD aided nonsurgical periodontal therapy. |
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[50] | ELISA | MMP-8, TIMP-1 | To determine the effect of azithromycin in addition to scaling and root planning in the treatment of periodontal disease. | Azithromycin did not present any advantage over scaling and root planning. |
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[51] | ELISA | Mucosa-associated epithelial chemokine (CCL28), IL-8, IL-1β, TNF-α | To determine the concentrations of CCL28, IL-1β, IL-8, and TNF-α in GCF among study groups. | CCL28, IL-1β, IL-8, and TNF-α concentrations were elevated in accordance with the severity of periodontal disease. |
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[52] | Flow cytometry | TNF-α, IL-1β, -6, -8, -10, -12p70 | To estimate the outcome of periodontal treatment on GCF and serum concentrations of many cytokines related with periodontal disease and premature birth. | GCF cytokine level reduced significantly after periodontal treatment. |
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[53] | MPBI, ELISA | Pentraxin 3, IL-10, -1β, -6, -8, TNFα | To estimate the correlation between clinical periodontal measurements and the concentrations of six cytokines. | There was a strong correlation between periodontal status and PTX3 or IL-1β levels in GCF. |
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[54] | ELISA | MDA, SOD, melatonin | To determine GCF concentrations of superoxide dismutase (SOD), malondialdehyde (MDA), and melatonin in GAgP and CP patients as oxidative stress biomarkers. | SOD, melatonin, and MDA could be used to differentiate between GAgP and CP patients. |
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[55] | Fluorometric kits | MMP-1, MMP-2, MMP-3, MMP-8, MMP-9, MMP-12, MMP-13 | To measure GCF MMPs levels after localized aggressive periodontitis (LAgP) treatment. | LAgP treatment with SRP and systemic antibiotics was active in reducing local levels of specific MMPs. |
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[56] | ELISA | MMP-8, MMP-9, MMP-13 | To evaluate whether the presence of periodontitis and metabolic syndrome was related to MMP in GCF in the Korean community. | MMP (-13, -8, -9) individually correlated to the presence of periodontitis and metabolic syndrome. |
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[57] | Western immunoblot | MMP-13 | To determine the role of GCF MMP-13 in adult CP patients. | There was significant increase in MMP-13 action in advanced periodontal disease. |
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[58] | ELISA | IL-23 | To determine GCF IL-23 levels in healthy subjects and patients with periodontal disease. | IL-23 levels increased correspondingly to periodontal disease progression. |
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[59] | ELISA | TNFα, soluble TNF receptors 1 and 2 | To evaluate TNF-α level, soluble TNF receptors 1 and 2 in serum and GCF of healthy and CP patients. | The levels between the two TNF receptors were disproportionate. |
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[60] | ELISA, immunoturbidimetric analysis | Stem cell factor (SCF), high-sensitivity C-reactive protein (hs-CRP) | To determine the relation between GCF and serum concentration of hs-CRP and SCF of two CP groups of which one is with T2DM and the other is without. | SCF and hs-CRP concentrations increased in patients with T2DM. |
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[61] | ELISA | Calprotectin | To evaluate the levels of calprotectin in GCF in GAgP patients prior to and after periodontal treatment. | Levels of calprotectin were indicators of disease activity in both subject and site levels. |
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[62] | ELISA | Myeloperoxidase (MPO), calprotectin | To observe calprotectin levels in GCF during therapy for GAgP. To determine a correlation between the MPO and calprotectin which were also determined. | Levels of calprotectin in GCF correlated to periodontal disease severity and decreased in concentration after treatment. |
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[63] | HPLCG | Platelet activating factor (PAF) | To determine the correlation between PAF and periodontal healing. | Alterations in PAF levels in GCF might be valuable for observing the regeneration and repair of periodontal tissues. |
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[64] | ELISA | chondroitin sulfate (CS), ALP | To determine the role of CS, ALP levels in estimating different periodontal disease stages. | The level of CS was better than the ALP level for determining periodontal disease stages. |
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[65] | ELISA | CS WF6 epitope | To evaluate GCF levels of CS WF6 epitope in healthy and periodontally diseased patients. | CS WF6 epitope levels positively correlated to the advancement of periodontal disease. |
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[66] | ELISA | MMP-8, -9, OPG, CRP, IL-1β | To evaluate the performance of MMP-8, -9, OPG, CRP, and IL-1β levels in GCF as a biomarker for periodontal disease. | MMP-8, -9, OPG, CRP, and IL-1β levels could support clinical parameters in the diagnosis of periodontal disease. |
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[67] | ELISA | IL-1β, IL-8, MMP-8 | To evaluate the influence of SRP on levels of cytokines in GCF from CP patients, in relation to clinical parameters. | SRP reduced the IL-8, IL-1β, and MMP-8 GCF levels. |
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[68] | ELISA | MMP-8 | To determine the association between MMP-8 in GCF and the severity of periodontal disease. | The level of active MMP-8 was higher in sites with deeper pocket depth. |
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[69] | ELISA, immunoturbidimetry | MCP-4, hs-CRP | To investigate GCF and serum levels of hs-CRP and MCP-4 among healthy and periodontally diseased patients. | hs-CRP and MCP-4 levels increased from periodontal healthy to periodontitis. hs-CRP and MCP-4 could be biomarkers of inflammation in periodontal health and disease. |
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[70] | ELISA | MCP-1, TNF-α | To determine and correlate GCF levels of MCP-1 and TNF-α in CP and AgP patients. | GCF levels of MCP-1 and TNF-α showed positive correlation. |
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[71] | ELISA, fluorometric method | PGE2, thiobarbituric acid reactive substance (TBARS) | To evaluate the effects of SRP and flurbiprofen in smokers and nonsmokers in CP patients on two GCF biomarkers. | PGE2 and TBARS levels in smokers decreased more than in nonsmokers after the flurbiprofen intake. |
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[72] | IFMA | MMP-8 | To measure the levels of MMP-8 in GCF among two CP groups (smokers and nonsmokers). | The levels of MMP-8 could be used in the monitoring of periodontal diseases. |
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[73] | ELISA, IFMA | Azurocidin, chemokine ligand 5, MPO, TIMP-1 MMP-13, -14 | To determine the diagnostic accuracy of GCF biomarkers. To compare two analytical techniques used to measure MMP-8 levels. | Collagenolytic MMPs and myeloperoxidase (MPO) could be considered as good biomarkers for periodontal diseases. IFMA analytical method was more precise than ELISA. |
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[74] | ELISA, radioimmunoassay | 25-Hydroxy vitamin D3, osteocalcin, IL-1β, IL-6 | To investigate the effect of SRP on the levels of 25-hydroxy vitamin D3 and three other biomarkers in GAgP patients. | Periodontal treatment led to reduction in the levels of 25-hydroxy vitamin D3 and IL-1β. |
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[75] | ELISA | PGE2, IL-1, TNF-α | To estimate the effect of combining two antibacterial drugs in initial periodontal treatment on periodontal parameters and certain biomarkers in patients with aggressive periodontitis. | Both types of treatment had substantial effect on periodontal disease status. |
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[76] | ELISA, immunoblotting | hCAP18/LL37, CS | To quantify GCF levels of hCAP18/LL-37 and CS in healthy, CP, and AgP study groups. | A positive correlation between the CS and hCAP18/LL-37 levels was noted in CP patients only. |
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[77] | MMP-8 specific chair-side dip-stick test | MMP-8 | To determine the accuracy of MMP-8 specific analytical techniques. | This testing method could be useful to support clinical periodontal diagnosis. |
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[78] | ELISA, SPM | MMP-8, -9, TIMP-1, -2, MPO | To determine GCF levels of five biomarkers in healthy and CP patients before and after treatment. | The biomarker levels were greater in CP groups. Their levels reduced after treatment. |
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[79] | ELISA | LL-37 | To evaluate GCF LL-37 levels in control and periodontally diseased groups and the degree of LL-37 by GCF elements. | LL-37 was detected in both study groups. There was high degradation of LL-37 level, mainly in Porphyromonas gingivalis positive sites. |
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[80] | MPBI | Granulocyte macrophage colony stimulating factor (GM-CSF), interferon-γ (INF-γ), IL-10, IL-1β, IL-2, IL-6, TNF-α | To determine the outcome of periodontal treatment by monitoring the alterations in cytokine levels from GCF samples in GAgP patients. | The periodontal treatment led to an increase in IL-10 levels and reduced IL-1β and GM-CSF levels. |
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[81] | ELISA | 8-Hydroxydeoxyguanosine | To evaluate the effect of nonsurgical periodontal treatment on 8-hydroxydeoxyguanosine levels in GCF and saliva. | 8-Hydroxydeoxyguanosine in GCF could reveal the severity of periodontal disease. |
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[82] | MPBI | INF-γ, IL-4, IL-33, thymic stromal lymphopoietin (TSLP) | To measure GCF levels of TSLP, IFN-γ, IL-4, and IL-33 in healthy and periodontally diseased patients. | Levels of IFN-γ related to the site stage and not on the disease stage IL-4. TSLP levels were detected in a few patients, while IL-33 was not detected. |
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[83] | SPM | ALP | To explain the effect of nonsurgical periodontal treatment on ALP action in GCF among CP patients. | ALP showed high activity following periodontal treatment, but after 60 days the ALP action reduced. |
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[84] | ELISA | IL-1β, TNF-α, MMP-8, MMP-9 | To determine the effect of nonsurgical periodontal treatment together with photodynamic therapy (PDT) on periodontal conditions in CP patients. | The use of PDT did not show any benefit in nonsurgical periodontal treatment. |
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[85] | ELISA | Visfatin | To identify the existence of visfatin in serum and GCF. | The level of visfatin increased in relation to the severity of periodontal disease. |
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[86] | ELISA | 8-Isoprostane | To measure 8-isoprostane concentrations in GCF in different periodontal diseases. | 8-Isoprostane concentrations elevated in accordance with periodontal disease progression. |
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[87] | ELISA, RANDOX analyzer | Progranulin, hs-CRP | To measure GCF and serum levels of progranulin and hs-CRP in control subjects, CP and CP with T2DM patients. | CP with T2DM patients showed more hs-CRP and PGRN levels than the other groups. |
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[88] | ELISA | MMP-9, MMP-8 | To measure GCF MMP-9 and MMP-8 levels in healthy subjects and patients with periodontal disease. | GCF MMP-9 and MMP-8 showed elevated levels in periodontally diseased patients. |
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[89] | ELISA | MMP-2, MMP-8 | To measure GCF levels of MMP-9 and MMP-2, and the MMP-8 levels in saliva among control subjects and patients with periodontal diseases. | All the types of MMP were found to be associated with clinical parameters. |
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[90] | ELISA, Western blot radioimmunoassay | IL-1β, MMP-8, bone resorption marker carboxyterminal telopeptide cross-link fragment of type I collagen (ICTP), total collagenase activity | To discover the association between specific biomarkers in GCF with bone resorption clinical parameters. | The biomarkers were associated with clinical attachment loss. |
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[91] | MPBI | IL-1α, -1β, -6, -10, TNF-α | To measure the total GCF levels of six cytokines in patients with periodontal disease before and after nonsurgical periodontal therapy. | Nonsurgical periodontal treatment resulted in reduced IL-1β, -1α and IL-6 levels. Nonetheless, TNF-α or IL-10 levels were not decreased. |
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[92] | MPBI | IL-1β, IL-4, IL8, elastase activity | To observe differences in clinical, immunologic, and microbiologic responses to SRP in patients with different periodontal diseases. | SRP resulted in nonsignificant differences between severe forms of CP and GAgP. |
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[93] | ELISA | IL-1β, IL-8, MMP-8, MMP-9 | To measure the concentration of specific biomarkers in GCF and the bacterial compositions in dental plaque in patients with and without type 1 diabetes (T1DM). | IL-1β and MMP-8 concentrations were found to be more elevated in patients with T1DM. |
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[94] | ELISA | IFN-γ, IL-23, IL-4, IL-17, TNF-α, OPG, RANKL | To determine the outcome of complete mouth SRP and noncomplete mouth SRP on cytokines levels and on clinical parameters over a twelve-month period. | Both types of treatment showed improvement in clinical parameters and the same changes in cytokines at twelve months. |
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[95] | ELISA | RANKL, OPG | To determine OPG and RANKL levels in GCF in patients with CP and AgP, as well as healthy subjects. | RANKL was present in periodontitis sites, especially in moderate periodontitis patients, whereas OPG was not noticeable in some sites with bleeding on probing. |
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[96] | IFMA, MMP-8 specific chair-side dip-stick test, DentoAnalyzer Device, ELISA | MMP-8 | To compare 4 techniques used for MMP-8 analysis. | DentoAnalyzer Device, IFMA and chair-side dip-stick test had the same detection ability, while dip-stick test appeared to be better. |
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[97] | ELISA | OPG, sRANKL | To determine GCF levels of the soluble RANKL and OPG in smokers with periodontal disease. | Smoking suppressed OPG production and led to increased sRANKL∖OPG. |
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[98] | Checkerboard immunoblotting | IL-1β, IL-8, MMP-8 | To investigate GCF levels of three cytokines and the microbial composition of the subgingival biofilm in control group and patients with periodontitis. | There were more cytokines and bacteria in the nondiseased sites in patients with periodontal diseases than there were in healthy individuals. |
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[99] | MPBI | GM-CSF, IL-2, -10, -13, -6, -1β, TNF-α, IFN-γ | To observe the relation between subgingival bacterial species and GCF cytokine concentrations in periodontal health and GAgP. | GAgP patients showed elevated ratio of IL-1β/IL-10 compared to the control group. |
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[100] | ELISA, Erels’ colorimetric method | IL-1β, TOS, total antioxidant status (TAS) | To investigate the smoking outcome on the relationship between oxidation and IL-1 in periodontitis patients and response to nonsurgical periodontal therapy. | SRP impacted IL-1β concentrations in GCF, while no effect was detected on the TAS and TOS. |
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[101] | ELISA | hs-CRP | To measure the concentrations of hs-CRP in GCF and serum in periodontally diseased patients in the presence and absence of coronary artery disease (CAD). | Both periodontally diseased groups showed higher Hs-CRPHs-CRP concentrations than did the control group. |
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[102] | MPBI | IL-2, 12(p70), -3, -4, -5, -10, -13, -1α, -1β, -6, -12(p40), -8, -7, -15, IP-10, MCP-1, MIP-1α, RANTES, eotaxin, IFN-γ, GM-CSF, TNF-α | To investigate the existence of GCF biomarkers among smokers and nonsmokers with and without periodontal disease. | Periodontitis patients showed increased biomarker profiles. Smoking led to a reduction in many chemokines and cytokines. |
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[103] | ELISA | Cystatin C, IL-1β, TNF-α | To determine cystatin C levels, IL-1β, and TNF-α in the GCF and saliva of periodontally healthy children (PHC) and children with gingivitis. | GCF and saliva cystatin C levels were higher in PHC, but there was no correlation between cystatin C levels and TNF-α or IL-1β levels in GCF or saliva. |
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[104] | ELISA | TNF-α, IL-4, INF-γ, IL-23, IL-17, sRANKL, OPG | To determine GCF levels of six biomarkers in CP patients with and without T2DM. | CP patients with T2DM showed more biomarker levels than did nondiabetic patients. |
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