Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: UMLS:C0031099 (periodontitis)
 12,489 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Certain human lymphocyte antigen (HLA) haplotypes have been correlated with the presence of certain diseases. To date no significant relationship between periodontitis and HLA haplotype has been demonstrated. The purpose of this study was to determine the frequency of HLA-A, HLA-B and HLA-C haplotypes in patients resistant to chronic periodontitis and to determine if there is any association between specific HLA genes and periodontal health. Twenty-five healthy individuals who demonstrated a high resistance to periodontal disease (mean age 49.9 years) were matched to 25 subjects with chronic periodontitis and to a periodontally undiagnosed population of 22,000 individuals. Peripheral blood was taken and HLA specificity was determined by the microlymphocytotoxicity test. The results indicated a statistically significant increase in the occurrence of HLA-B5 (P = 0.0059) and a trend in the occurrence of HLA-A28 (P = 0.0565) in those patients resistant to periodontal disease when compared to the matched controls. When compared to the large random control group, a significant correlation was observed for HLA-A28 (P less than 0.01) in blacks and HLA-B5 (P less than 0.01) in whites. It is possible that the HLA-A28 and the HLA-B5 individual may have the ability to resist the progression of chronic periodontitis.
 ...
PMID:Human lymphocyte antigen haplotype and resistance to periodontitis. 658 91

A bacterial etiology of rheumatoid arthritis (RA) has been suspected since the beginnings of modern germ theory. Recent studies implicate mucosal surfaces as sites of disease initiation. The common occurrence of periodontal dysbiosis in RA suggests that oral pathogens may trigger the production of disease-specific autoantibodies and arthritis in susceptible individuals. We used mass spectrometry to define the microbial composition and antigenic repertoire of gingival crevicular fluid in patients with periodontal disease and healthy controls. Periodontitis was characterized by the presence of citrullinated autoantigens that are primary immune targets in RA. The citrullinome in periodontitis mirrored patterns of hypercitrullination observed in the rheumatoid joint, implicating this mucosal site in RA pathogenesis. Proteomic signatures of several microbial species were detected in hypercitrullinated periodontitis samples. Among these, Aggregatibacter actinomycetemcomitans (Aa), but not other candidate pathogens, induced hypercitrullination in host neutrophils. We identified the pore-forming toxin leukotoxin A (LtxA) as the molecular mechanism by which Aa triggers dysregulated activation of citrullinating enzymes in neutrophils, mimicking membranolytic pathways that sustain autoantigen citrullination in the RA joint. Moreover, LtxA induced changes in neutrophil morphology mimicking extracellular trap formation, thereby releasing the hypercitrullinated cargo. Exposure to leukotoxic Aa strains was confirmed in patients with RA and was associated with both anticitrullinated protein antibodies and rheumatoid factor. The effect of human lymphocyte antigen-DRB1 shared epitope alleles on autoantibody positivity was limited to RA patients who were exposed to Aa These studies identify the periodontal pathogen Aa as a candidate bacterial trigger of autoimmunity in RA.
 ...
PMID:Aggregatibacter actinomycetemcomitans-induced hypercitrullination links periodontal infection to autoimmunity in rheumatoid arthritis. 2956 22