The Role of Spirochetes in Periodontal Disease

The spirochetal accumulation in subgingival plaque appears to be a function of the clinical severity of periodontal disease. It is not known how many different spirochetal species colonize the plaque, but based upon size alone, there are small, intermediate-sized, and large spirochetes. Four species of small spirochetes are cultivable, and of these, T. denticola has been shown to possess proteolytic and keratinolytic enzymes as well as factors or mechanisms which suppress lymphocyte blastogenesis and inhibit fibroblast and polymorphonuclear leukocyte (PMNL) function. All of these attributes could contribute to periodontal tissue insult. Yet independent of these potential virulence mechanisms, the overgrowth of spirochetes can be clinically useful if simply interpreted as indicating the result of tissue damage. In this case, the spirochetes would be indicators of disease and could be easily monitored by microscopic examination of plaque, or possibly by the measurement of benzoyl-DL-arginine-2-naphthylamide (BANA) hydrolytic activity in the plaque.Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/68092/2/10.1177_08959374880020021201.pd

Oral Fluid–Based Biomarkers of Alveolar Bone Loss in Periodontitis

Periodontal disease is a bacteria-induced chronic inflammatory disease affecting the soft and hard supporting structures encompassing the teeth. When left untreated, the ultimate outcome is alveolar bone loss and exfoliation of the involved teeth. Traditional periodontal diagnostic methods include assessment of clinical parameters and radiographs. Though efficient, these conventional techniques are inherently limited in that only a historical perspective, not current appraisal, of disease status can be determined. Advances in the use of oral fluids as possible biological samples for objective measures of current disease state, treatment monitoring, and prognostic indicators have boosted saliva and other oral-based fluids to the forefront of technology. Oral fluids contain locally and systemically derived mediators of periodontal disease, including microbial, host-response, and bone-specific resorptive markers. Although most biomarkers in oral fluids represent inflammatory mediators, several specific collagen degradation and bone turnover-related molecules have emerged as possible measures of periodontal disease activity. Pyridinoline cross-linked carboxyterminal telopeptide (ICTP), for example, has been highly correlated with clinical features of the disease and decreases in response to intervention therapies, and has been shown to possess predictive properties for possible future disease activity. One foreseeable benefit of an oral fluid–based periodontal diagnostic would be identification of highly susceptible individuals prior to overt disease. Timely detection and diagnosis of disease may significantly affect the clinical management of periodontal patients by offering earlier, less invasive, and more cost-effective treatment therapies.Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/73247/1/annals.1384.028.pd

Correlates of protective cellular immunity revealed by analysis of population-level immune escape pathways in HIV-1

HLA class I-associated polymorphisms identified at the population level mark viral sites under immune pressure by individual HLA alleles. As such, analysis of their distribution, frequency, location, statistical strength, sequence conservation, and other properties offers a unique perspective from which to identify correlates of protective cellular immunity. We analyzed HLA-associated HIV-1 subtype B polymorphisms in 1,888 treatment-naïve, chronically infected individuals using phylogenetically informed methods and identified characteristics of HLA-associated immune pressures that differentiate protective and nonprotective alleles. Over 2,100 HLA-associated HIV-1 polymorphisms were identified, approximately one-third of which occurred inside or within 3 residues of an optimally defined cytotoxic T-lymphocyte (CTL) epitope. Differential CTL escape patterns between closely related HLA alleles were common and increased with greater evolutionary distance between allele group members. Among 9-mer epitopes, mutations at HLA-specific anchor residues representedthe most frequently detected escape type: these occurred nearly 2-fold more frequently than expected by chance and were computationally predicted to reduce peptide-HLA binding nearly 10-fold on average. Characteristics associated with protective HLA alleles (defined using hazard ratios for progression to AIDS from natural history cohorts) included the potential to mount broad immune selection pressures across all HIV-1 proteins except Nef, the tendency to drive multisite and/or anchor residue escape mutations within known CTL epitopes, and the ability to strongly select mutations in conserved regions within HIV's structural and functional proteins. Thus, the factors defining protective cellular immune responsesmay be more complex than simply targeting conserved viral regions. The results provide new information to guide vaccine design and immunogenicity studies