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局限性侵袭性牙周炎的局部和血浆生物标志物谱

Local and Plasma Biomarker Profiles in Localized Aggressive Periodontitis.

作者信息

Branco-de-Almeida L S, Cruz-Almeida Y, Gonzalez-Marrero Y, Huang H, Aukhil I, Harrison P, Wallet S M, Shaddox L M

机构信息

Department of Periodontology, College of Dentistry, University of Florida, Gainesville, FL, USA.

Department of Dentistry II, School of Dentistry, Federal University of Maranhão, São Luís, Brazil.

出版信息

JDR Clin Trans Res. 2017 Jul;2(3):258-268. doi: 10.1177/2380084417701898. Epub 2017 Apr 14.

Abstract

Localized aggressive periodontitis (LAP) patients possess a systemic hyperinflammatory response after lipopolysaccharide stimulation. However, the levels of inflammatory and bone biomarkers in plasma, as well as possible associations between local and plasma biomarkers, are unknown in LAP. This cross-sectional study aimed to characterize gingival crevicular fluid (GCF) and plasma biomarker profiles in LAP patients, their healthy siblings (HS), and healthy unrelated controls (HC). Fifty-eight LAP subjects, 33 HS, and 49 HC (African Americans, aged 5 to 25 y) were included. Following collection of clinical parameters with GCF and plasma samples, levels of 16 inflammatory and bone resorption biomarkers were determined with Milliplex. Univariate and correlation analyses were performed among all clinical and laboratorial parameters. Discriminant analyses were used to investigate groups of biomarkers discriminating LAP from HS and HC in GCF and plasma. GCF levels of multiple cytokines and chemokines and RANKL:OPG ratio (receptor activator of nuclear factor kappa-B ligand:osteoprotegerin) were higher in LAP disease, most of which positively correlated with probing depth and attachment loss of sampled sites. A group of IL-12p40, IL-6, IL-12p70, IL-2, and MIP-1α discriminated LAP diseased sites from twheir healthy sites, as well as from HS and HC healthy sites. In plasma, only RANKL levels were increased in LAP versus controls, which positively correlated with the percentage of affected sites and deep/bleeding sites. A plasma inflammatory profile including MIP-1α, IL-8, IL-10, and INF-γ could significantly discriminate LAP patients from HS and HC. No correlations were found between GCF and plasma levels of biomarkers. In conclusion, an inflammatory profile including groups of specific biomarkers in GCF and plasma may significantly discriminate LAP from healthy individuals. The hyperinflammatory response previously found in the peripheral blood of LAP patients is dependent on lipopolysaccharide stimulation, apparently resulting mostly in local tissue destruction and changes in biomarker profile, with a slight influence in the systemic inflammatory profile (ClinicalTrials.gov NCT01330719). The results of this study can be possibly used by clinicians in the future as diagnostic tools for localized aggressive periodontitis. Thus, in the future, with proper consideration of cost, patient preference, chair-side feasibility and ultimately further studies validating the role of GCF markers for disease progression and response to treatment, this information could lead to more appropriate therapeutic decisions and the development of preventive approaches for susceptible patients.

摘要

局限性侵袭性牙周炎(LAP)患者在脂多糖刺激后会出现全身高炎症反应。然而,LAP患者血浆中炎症和骨生物标志物的水平,以及局部和血浆生物标志物之间可能存在的关联尚不清楚。这项横断面研究旨在描述LAP患者、其健康同胞(HS)和健康非亲属对照(HC)的龈沟液(GCF)和血浆生物标志物谱。纳入了58名LAP受试者、33名HS和49名HC(非裔美国人,年龄5至25岁)。在采集GCF和血浆样本的临床参数后,用Milliplex测定16种炎症和骨吸收生物标志物的水平。对所有临床和实验室参数进行单变量和相关性分析。采用判别分析研究在GCF和血浆中区分LAP与HS和HC的生物标志物组。LAP疾病中多种细胞因子和趋化因子的GCF水平以及RANKL:OPG比值(核因子κB受体活化剂配体:骨保护素)较高,其中大多数与采样部位的探诊深度和附着丧失呈正相关。一组IL-12p40、IL-6、IL-12p70、IL-2和MIP-1α可区分LAP病变部位与其健康部位,以及HS和HC健康部位。在血浆中,与对照组相比,LAP患者仅RANKL水平升高,且与患牙部位及深/出血部位的百分比呈正相关。包括MIP-1α、IL-8、IL-10和INF-γ的血浆炎症谱可显著区分LAP患者与HS和HC。未发现生物标志物的GCF水平与血浆水平之间存在相关性。总之,包括GCF和血浆中特定生物标志物组的炎症谱可能显著区分LAP与健康个体。先前在LAP患者外周血中发现的高炎症反应依赖于脂多糖刺激,显然主要导致局部组织破坏和生物标志物谱的变化,对全身炎症谱影响较小(ClinicalTrials.gov NCT01330719)。本研究结果未来可能被临床医生用作局限性侵袭性牙周炎的诊断工具。因此,未来在适当考虑成本、患者偏好、椅旁可行性以及最终进一步研究验证GCF标志物在疾病进展和治疗反应中的作用后,这些信息可能会导致更合适的治疗决策,并为易感患者开发预防方法。

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