Fine Daniel H, Markowitz Kenneth, Fairlie Karen, Tischio-Bereski Debbie, Ferrandiz Javier, Godboley Dipti, Furgang David, Gunsolley John, Best Al
Department of Oral Biology, School of Dental Medicine, Rutgers University, Newark, New Jersey, United States of America.
Department of Periodontics, School of Dentistry, Virginia Commonwealth of Virginia, Richmond, Virginia, United States of America.
PLoS One. 2014 Jun 5;9(6):e98541. doi: 10.1371/journal.pone.0098541. eCollection 2014.
Improved diagnostics remains a fundamental goal of biomedical research. This study was designed to assess cytokine biomarkers that could predict bone loss (BL) in localized aggressive periodontitis. 2,058 adolescents were screened. Two groups of 50 periodontally healthy adolescents were enrolled in the longitudinal study. One group had Aggregatibacter actinomycetemcomitans (Aa), the putative pathogen, while the matched cohort did not. Cytokine levels were assessed in saliva and gingival crevicular fluid (GCF). Participants were sampled, examined, and radiographed every 6 months for 2-3 years. Disease was defined as radiographic evidence of BL. Saliva and GCF was collected at each visit, frozen, and then tested retrospectively after detection of BL. Sixteen subjects with Aa developed BL. Saliva from Aa-positive and Aa-negative healthy subjects was compared to subjects who developed BL. GCF was collected from 16 subjects with BL and from another 38 subjects who remained healthy. GCF from BL sites in the 16 subjects was compared to healthy sites in these same subjects and to healthy sites in subjects who remained healthy. Results showed that cytokines in saliva associated with acute inflammation were elevated in subjects who developed BL (i.e., MIP-1α MIP-1β IL-α, IL-1β and IL-8; p<0.01). MIP-1α was elevated 13-fold, 6 months prior to BL. When MIP-1α levels were set at 40 pg/ml, 98% of healthy sites were below that level (Specificity); whereas, 93% of sites with BL were higher (Sensitivity), with comparable Predictive Values of 98%; p<0.0001; 95% C.I. = 42.5-52.7). MIP-1α consistently showed elevated levels as a biomarker for BL in both saliva and GCF, 6 months prior to BL. MIP-1α continues to demonstrate its strong candidacy as a diagnostic biomarker for both subject and site vulnerability to BL.
改进诊断方法仍然是生物医学研究的一个基本目标。本研究旨在评估可预测局限性侵袭性牙周炎骨丧失(BL)的细胞因子生物标志物。对2058名青少年进行了筛查。两组各50名牙周健康的青少年被纳入纵向研究。一组携带假定病原体伴放线聚集杆菌(Aa),而匹配的队列则未携带。对唾液和龈沟液(GCF)中的细胞因子水平进行了评估。参与者每6个月进行一次采样、检查和X光检查,持续2至3年。疾病定义为有骨丧失的影像学证据。每次就诊时收集唾液和GCF,冷冻保存,然后在检测到骨丧失后进行回顾性检测。16名携带Aa的受试者出现了骨丧失。将Aa阳性和Aa阴性健康受试者的唾液与出现骨丧失的受试者的唾液进行了比较。从16名出现骨丧失的受试者和另外38名保持健康的受试者中收集了龈沟液。将这16名受试者骨丧失部位的龈沟液与这些受试者的健康部位以及保持健康的受试者的健康部位进行了比较。结果显示,出现骨丧失的受试者(即MIP-1α、MIP-1β、IL-α、IL-1β和IL-8;p<0.01)唾液中与急性炎症相关的细胞因子水平升高。骨丧失前6个月,MIP-1α升高了13倍。当MIP-1α水平设定为40 pg/ml时,98%的健康部位低于该水平(特异性);而93%的骨丧失部位高于该水平(敏感性),预测值相当,为98%;p<0.0001;95%置信区间=42.5-52.7)。在骨丧失前6个月,MIP-1α在唾液和龈沟液中均持续显示出作为骨丧失生物标志物的升高水平。MIP-1α继续证明其作为受试者和部位易发生骨丧失的诊断生物标志物的强大潜力。