Correlation of serum cytokines, chemokines, growth factors and enzymes with periodontal disease parameters
Correlation of serum cytokines, chemokines, growth factors and enzymes with periodontal disease parameters
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DOI：
10.1371/journal.pone.0188945
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发表时间：
2017-11-30
期刊：
影响因子：
3.7
通讯作者：
Larsson, Anders
中科院分区：
文献类型：
--
作者：
Panezai, Jeneen;Ghaffar, Ambereen;Larsson, Anders
牙周病是以牙齿支持器炎性组织破坏为特征的疾病。许多研究表明，类风湿关节炎(RA)的潜在发病机制与免疫炎症事件共同影响这两种疾病是一致的。本研究旨在探讨PD和RA患者血清细胞因子、趋化因子、生长因子、酶和共刺激蛋白与牙周状况的关系。材料与方法对RA(n=38)、PD(n=38)和健康人(n=14)进行牙周检查。测量探诊出血量(BOP)和探诊袋深(PPD)。在数字化全景片上测量前磨牙和磨牙的边缘骨丢失(MBL)。如果PPD=5 mm，在>；=3个不同部位，则定义为存在PPD。血清样本采集自所有受试者。采用多重邻近延伸分析(PEA)同时检测92种细胞因子。结果ST1A1、FGF19和NT-3的表达与牙周炎的发生呈显著正相关，而ENRAGE、DNER、CX3CL1和TWEE与BOP、PPD和GT；=5 mm、MBL呈负相关，而与牙数呈正相关。CD244、CD40、CDCP1、LIF-R、IL-10RA、CD5和CD6等CD标志物与BOP、浅袋和深袋、MBL和牙数呈正相关或负相关。大多数趋化因子(CCL8、CX3CL1、CXCL10、CXCL11、CCL11、CCL4、CCL20、CXCL5、CXCL6和CCL23)与牙数呈正相关，与MBL呈负相关(CCL8、CXCL10)。具有酶活性的蛋白(ST1A1、HGF和CASP-8)与牙周疾病的严重程度直接相关，与牙数呈负相关。除成纤维细胞生长因子-19外，其他生长因子也与牙周膜厚度(HGF)、牙数(VEGF-A、LAP转化生长因子-β1)直接相关，与浅袋(LAP转化生长因子-β1、TGFA和β-NGF)成反比。在33个细胞因子中，32个与浅眼袋呈负相关，而只有CD40呈正相关。类风湿性关节炎患者细胞因子与牙周参数的相关性相对较低。采用Benjamini-Hochberg错误发现率方法对多变量效应进行统计分析。结论系统性炎症负荷通过已知和新的标记物与PD和RA受试者的牙周状况相关。浅眼袋与更高的炎症状态无关。
BackgroundPeriodontal disease (PD) is characterized by inflammatory tissue destruction in tooth supporting apparatus. Many studies indicate that the underlying pathogenesis is in concordance with rheumatoid arthritis (RA) sharing immune-inflammatory events affect both diseases. The aim of this study was to investigate serum cytokines, chemokines, growth factors, enzymes and costimulatory proteins in association with periodontal conditions in PD and RA subjects.Materials & methodsPeriodontal examination was performed in RA (n = 38), PD (n = 38) and healthy subjects (n = 14). Bleeding on probing (BOP) and probing pocket depth (PPD) were measured. Marginal bone loss (MBL) for premolars and molars was measured on digital panoramic radiographs. PD was defined as present if the PPD was >= 5mm in >= 3 different sites. Serum samples were collected from all subjects. A multiplex proximity extension assay (PEA) was used to analyze the samples for simultaneous measurement of 92 cytokines. Cytokines with >= 60% quantitative results were included.ResultsA significant positive correlation was seen for ST1A1, FGF-19 and NT-3 whereas EN-RAGE, DNER, CX3CL1 and TWEAK associated inversely with BOP, PPD >= 5mm and MBL but positively with number of teeth. Several CD markers (CD244, CD40, CDCP1, LIF-R, IL-10RA, CD5 and CD6) were found to be associated with BOP, shallow and deep pockets, MBL and number of teeth, either directly or inversely. Most chemokines (CCL8, CX3CL1, CXCL10, CXCL11, CCL11, CCL4, CCL20, CXCL5, CXCL6, and CCL23) were positively associated with number of teeth and some inversely related to MBL (CCL8, CXCL10). Proteins with enzymatic activity (ST1A1, HGF and CASP-8) were directly related to the severity of periodontal conditions and inversely related to number of teeth. Aside from FGF-19, other growth factors were also directly associated with MBL (HGF), number of teeth (VEGF-A, LAP TGF-beta-1) and, inversely to, shallow pockets (LAP TGF-beta-1, TGFA and Beta-NGF). Out of 33 cytokines, 32 associated inversely with shallow pockets, whereas only CD40 associated positively. Associations between cytokines and periodontal parameters in the RA group were comparatively less. Statistical analyses were adjusted for multivariate effects using the Benjamini-Hochberg false discovery rate method.ConclusionSystemic inflammatory burden, via known and novel markers, is associated with periodontal conditions in PD and RA subjects. Shallow pockets are not associated with a higher inflammatory state.