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.

Agency
National Institute of Health (NIH)
Institute
National Institute of Dental & Craniofacial Research (NIDCR)
Type
Research Project (R01)
Project #
5R01DE017968-04
Application #
7871397
Study Section
Oral, Dental and Craniofacial Sciences Study Section (ODCS)
Program Officer
Nowjack-Raymer, Ruth
Project Start
2007-07-15
Project End
2012-06-30
Budget Start
2010-07-01
Budget End
2011-06-30
Support Year
4
Fiscal Year
2010
Total Cost
$685,675
Indirect Cost
Name
University of Medicine & Dentistry of NJ
Department
Dentistry
Type
Schools of Dentistry
DUNS #
781265475
City
Newark
State
NJ
Country
United States
Zip Code
07101
Cugini, Carla; Mei, Yongyi; Furgang, David et al. (2018) Utilization of Variant and Fusion Proteins To Functionally Map the Aggregatibacter actinomycetemcomitans Trimeric Autotransporter Protein ApiA. Infect Immun 86:
Velusamy, Senthil K; Sampathkumar, Vandana; Godboley, Dipti et al. (2017) Survival of an Aggregatibacter actinomycetemcomitans quorum sensing luxS mutant in the mouths of Rhesus monkeys: insights into ecological adaptation. Mol Oral Microbiol 32:432-442
Fine, D H (2015) Lactoferrin: A Roadmap to the Borderland between Caries and Periodontal Disease. J Dent Res 94:768-76
Fine, Daniel H; Markowitz, Kenneth; Fairlie, Karen et al. (2014) Macrophage inflammatory protein-1? shows predictive value as a risk marker for subjects and sites vulnerable to bone loss in a longitudinal model of aggressive periodontitis. PLoS One 9:e98541
Fine, Daniel H; Markowitz, Kenneth; Fairlie, Karen et al. (2013) A consortium of Aggregatibacter actinomycetemcomitans, Streptococcus parasanguinis, and Filifactor alocis is present in sites prior to bone loss in a longitudinal study of localized aggressive periodontitis. J Clin Microbiol 51:2850-61
Velusamy, S K; Ganeshnarayan, K; Markowitz, K et al. (2013) Lactoferrin knockout mice demonstrates greater susceptibility to Aggregatibacter actinomycetemcomitans-induced periodontal disease. J Periodontol 84:1690-701
Schreiner, Helen; Li, Yu; Cline, Joshua et al. (2013) A comparison of Aggregatibacter actinomycetemcomitans (Aa) virulence traits in a rat model for periodontal disease. PLoS One 8:e69382
Fine, Daniel H; Furgang, David; McKiernan, Marie et al. (2013) Can salivary activity predict periodontal breakdown in A. actinomycetemcomitans infected adolescents? Arch Oral Biol 58:611-20
Genderson, M W; Sischo, L; Markowitz, K et al. (2013) An overview of children's oral health-related quality of life assessment: from scale development to measuring outcomes. Caries Res 47 Suppl 1:13-21
Fine, Daniel H; Toruner, Gokce A; Velliyagounder, Kabilan et al. (2013) A lactotransferrin single nucleotide polymorphism demonstrates biological activity that can reduce susceptibility to caries. Infect Immun 81:1596-605

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