Localized Aggressive Periodontitis (LAP) affects approximately 70,000 U.S. children, largely from underserved groups. If untreated, LAP can lead to loss of first molars and central incisors. The proposal expands on preliminary data and surveys microbial and host factors indicative of LAP risk. This study will screen 3,000 periodontally healthy children from Newark for the presence of Actinobacillus actiinomycetemcomitans (Aa). 205 test (Aa+) and 410 control (Aa-) will be recalled at 6-month intervals for 4-5 yrs to identify factors predictive of disease onset. Screening and recall exams include a periodontal examination, collection of saliva and buccal cells as well as crevicular fluid and subgingival plaque from pocketed sites and the mesial of all 1st molars. Samples will be stored for future analysis. Horizontal bite- wing radiographs are used to establish the LAP diagnosis. When bone loss is detected, stored site-specific samples will be analyzed. The revised proposal includes 2 aims: 1. to determine whether Aa, clones of Aa, or 200 members of the flora associated with Aa could be predictive of the onset of LAP; 2. to examine host factors that can affect Aa colonization, persistence, subgingival migration and subsequent activation of innate and acquired immune factors associated with disease onset. These factors include: iron-saturation of lactoferrin, IgA antibody titers to Aa adhesins, a Growth Modifying Factor (GMF) that killls Gram+ pioneer plaque microbes that compete with Aa, IgG antibody levels to leukotoxin and levels of 21 cytokines that can affect disease initiation. Comparison of data from Aa+ (test) and Aa- (control) groups should provide information with which to determine the combination of microbial and host markers predictive of risk for LAP onset. To date in those recalled for 1yr or more, 7 of 36 Aa+ students have developed LAP, while none of the Aa- conrols have LAP (p <.01). Pilot data from saliva obtained from students recalled indicates the following; 1. GMF from Aa+ students can kill pioneer plaque microbes in vitro (p < .01), 2. lower IgA levels are found in students repeatedly colonized by Aa, and 3. a specific cytokine, MIP 1a, is significantly elevated in Aa+/LAP subjects prior to bone loss (p <.01). The knowledge gained from this prospective study should identify markers required to develop a salivary-based diagnostic test that can be used to design preventive strategies to reduce oral health disparities in this predominantly African American and Hispanic population. [unreadable] [unreadable] [unreadable]