Chemistry: molecular biology and microbiology – Measuring or testing process involving enzymes or... – Involving antigen-antibody binding – specific binding protein...
Reexamination Certificate
2000-08-24
2003-06-10
Devi, S. (Department: 1645)
Chemistry: molecular biology and microbiology
Measuring or testing process involving enzymes or...
Involving antigen-antibody binding, specific binding protein...
C435S007100, C435S007310, C435S007400, C435S007200
Reexamination Certificate
active
06576435
ABSTRACT:
BACKGROUND
Inflammatory adult periodontitis is a major cause of tooth loss in the middle aged and elderly. The gingival sulci of teeth become infected with a complex mixture of bacteria that impair tooth attachment. Mechanical debridement of the teeth-surfaces (scaling and root planing, SRP) is the current basis of prevention. Many patients preserve tooth attachment with regular SRP and home care, but some,.defined as refractory, continue to lose attachment, even after additional therapy, tetracycline and surgery, to supplement SRP efficacy [1,2]. The severity of prior attachment loss increases the likelihood that a patient will be refractory to therapy [3,4], as also does attachment loss in response to initial SRP [5]. The ability to identify refractory subjects at initial examination would provide several functions that are currently lacking in periodontics. It would indicate how patients should be divided to determine differences in host response or bacterial flora a priori, what patients would benefit most from new and experimental therapies and provide an objective criterion for periodontists to warn patients of failure before treatment is begun.
Although patients develop antibody responses to various bacterial antigens, responses to specific bacteria have not been related to disease severity or progression except in a general way. The odds ratio of being refractory increased from 3-fold to 19-fold as the number of bacterial taxa with an antibody concentration >50 &mgr;g/ml increased from 3 to 17, out of a total of 85 bacterial taxa examined [6]. Measuring antibody levels to 85 taxa is difficult. A more specific response was the antibody to
Hemophilus aphrophilus
being >50 &mgr;g/ml, but the rationale for measuring antibodies to this organism is not clear and a second, more complex laboratory procedure, measuring bacterial DNA to
Streptococcus constellatus
, is also required [6]. The proposed procedure requires only antibody levels, and clinical measurements that all periodontists obtain prior to therapy.
Recent findings suggest that, of 40 bacterial species detected in the sulci pre-therapy, 37% of the variance in attachment level change after initial SRP was predicted by only the amount of
Actinomyces naeslundii
serotype 2 and
Treponema denticola
[5
]. A. naeslundii
extrudes an ornithine-rich antigen that contains an epitope to which an IgG antibody is directed in human serum [7,8]. An antibody response to this Actinomyces antigen is increased in subjects with less plaque, gingivitis and caries [9]. The sulci of refractory patients contain increased numbers of constellatus/anginosus streptococci [2] that possess a streptococcal antigen (e.g., D-alanyl lipoteichoic acid (D-alanyl-LTA)), whereas mitis/oralis streptococci do not possess D-alanyl LTA and increase in healthy sulci [10,11].
Capnocytophaga sputigena
and
Capnocytophaga ochracea
are indigenous bacteria which, in addition to
Eikenella corrodens
, make lysine decarboxylase. When one or other of these bacteria comprise more than 2.5% of the total bacterial DNA from sulci, the odds ratios that the patient will be refractory is respectively increased 16-fold or 5.8 fold [6]. Lysine decarboxylase activity in healthy or recently cleaned sulci creates inflammation by irritating the dentally attached (DAT) cells of the oral epithelial attachment. Because therapy does not remove indigenous bacteria, increased numbers of bacteria such as
E. corrodens
or Capnocytophaga spp. in the indigenous flora will infect sulci after cleaning and their lysine decarboxylase production will prevent healthy DAT cells from becoming re-established.
E. corrodens
and Capnocytophaga spp. form most of a bacterial cluster group that colonizes healthy and recently cleaned sulci [12].
Subjects with advanced periodontitis (>4 mm attachment loss) are difficult to treat becasue of anatomical difficulties in keeping a low bacterial load [1], whereas subjects with mild disease are easy to treat successfully and inexpensively. The therapeutic response of subjects with moderate periodontitis is unpredictable. At present, the fraction of sulci that bleed when gently probed is the only criterion for whther a patient will be refractory. It is so unsatisfactory that, when periodontists are faced with treatment failure, they do not know whether this was inherent in the patient or the result of an overlooked problem [5]. The object of the present invention is therefore to enable prediction of which patients will be refractory after initial therapy so they can be warned that there is a high risk of treatment failing within two years thereby potentially enabling other treatment options to be identified or at least anticipated.
REFERENCES:
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Levine et al., Analysis of the Specificity of Natural Human Antibody Reactive to Actinomyces, Molecular Innumology, vol. 23, No. 3, pp 255-261, 1986.
Levine et al., Fast Elisa for Measuring Serum Antibody Responses, Journal of Immunological Methods, 119, pp 211-215, 1989.
Martin Levine, Naturally Occurring Human Serum Precipitins Specific For D-Alanyl Esters of Clycerol Teichoic Acid, Molecular Immunology, vol. 19, No. 1, pp 133-142, 1982.
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Jeffrey L. Ebersole, Systemic Humoral Immune Responses in Periodontal Disease, Oral Biology and Medicine, pp 283-331, 1990.
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Holmes et al., Unusual Gram-Negative Bacteria, Including Capnocytophaga, Eikenella, Pasteurella, and Streptobacullus, Bacteriology, 39, pp 499-508.
Sabo et al., Chemical Properties ofEscherichia ColiLysine Decarboxylase Including a Segment of its Pyridoxal 5'-Phosphate Binding Site, Biochemistry, vol. 13, No. 4, pp 670-676, 1974.
Phan et al., Spectrophotometric Assay for Lysine Decarboxylase, Analytical Biochemistry, 120, pp 193-197, 1982.
Hogg et al., Occurence of Lipoteichoic Acid in Oral Streptococci, Int. Journal of Systematic Bacteriology, pp 62-66, Jan. 1997.
Warren et al., Biosynthesis of D-Alanyl-Lipoteichoic Acid: Characterization of Ester-Linked D-Alanine in the in Vitro-Synthesized Product, Journal of Bacteriology, pp 293-301, Jul. 1980.
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