Abstract
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.
Highlights
Improved diagnostics has been a major initiative in all phases of health care for the last 20 years with the anticipation that early diagnosis will lead to effective preventive treatment, reduced medical expenses, and improved overall health [1,2]
Both soft and hard tissue measurements are downstream relative to disease initiation and represent past historical data. Notwithstanding these shortcomings identification of bone biomarkers in Localized Aggressive Periodontitis (LAP) could provide meaningful information for both forms of periodontal disease because the mechanisms for bone loss (BL) are host related, are common to both diseases (CAP and LAP), and should occur at least 6-months prior to detectable BL by radiograph [19]. Along these lines we have previously identified MIP-1a as a unique biomarker related to bone remodeling in LAP which has recently been confirmed by others in Chronic Adult Periodontitis (CAP) [20,21,22]
The overall goals of the study are to identify host and microbial biomarkers of disease development. The purpose of this current study is to identify both subject and sitespecific host-related biomarkers that could be predictive of BL in LAP subjects
Summary
Improved diagnostics has been a major initiative in all phases of health care for the last 20 years with the anticipation that early diagnosis will lead to effective preventive treatment, reduced medical expenses, and improved overall health [1,2]. Screening was performed to select a group of healthy Aa-positive and Aa-negative subjects for enrollment into a longitudinal study designed to assess the association of Aa-carriage to host and microbial factors related to development of LAP.
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