Tests of the Host Response—Risks

10.1055/b-0034-56513

Tests of the Host Response—Risks

  • Risk Factors

  • Severity Factors

  • Progression Factors

All of the tests described thus far are based on clinical parameters and directly or indirectly on the identification of periodontopathic bacteria. The tests described below provide indications of the host response to the microbial infection.

Many indicators can signal on-going periodontal destruction, including PMN defects, high titers of antibodies against periodontopathogens, enzymes such as aspartate aminotransferase (AST; Persson et al. 1995), elevated inflammatory mediators (PGE2) and others. Also, the measurement of subgingival temperature (e.g., PerioTemp System) can indicate the existence of inflammation, but not necessarily provide information about the progression of the disease (Kohlhurst et al. 1991, Fedi & Killoy 1992, Trejo et al. 1994).

None of the current methods for testing host response have yet achieved routine utilization in practice.

427 Enzyme Test—Hawe Periomonitor This practical test measures the amount of aspartate aminotransferase (AST) in the sulcus fluid. AST is an intracellular enzyme, which is released upon cell death and can therefore be correlated with the amount of tissue destruction. The test is based on a color reaction. Right: Sulcus fluid strips remain in situ for 30 seconds.
428 Subgingival Temperature – PerioTemp System (Abiodent, Inc.) Heat is one of the cardinal symptoms of inflammation (“calor”). The temperature at the base of a periodontal pocket can be measured using a fine, graduated, sterile temperature probe. The instrument provides a color scale depicting all 32 teeth, displaying green-red when the average subgingival temperature exceeds 35.5° C. The measured values can also be printed out (left).

Genetic Risk—Test for IL-1 Gene Polymorphism

In the chapter on etiology and pathogenesis (pp. 41–66) the enormous significance of the various host defense mechanisms against microbial infection was extensively portrayed. It was demonstrated that inflammatory reactions are regulated by numerous messenger substances and enzymes such as prostaglandins, metalloproteinases and certain cytokines. One of these cytokines is one of the most powerful general activators: Interleukin 1 (IL-1). It exists as IL-1α and IL-1β, whose production is coded for by the two genes IL-1A and IL-1B (both on chromosome 2).

IL-1 Gene Polymorphism

Mutations of an individual base pair (“single nucleotide polymorphism”; SNP) are quite common; the normal base sequence in the gene is termed Allele 1, and the less common or altered as Allele 2. Both IL-1 genes can exhibit the SNP: The base cytosine (pairing with guanine, (Fig. 430) is then replaced by thymine (pairing with adenine). Polymorphisms are not representative of major genetic alterations (gene defects, cf. p. 54), and their effects are therefore usually mild.

429 Differences in Monocyte Stimulation with IL-1-positive and IL-1-negative Genotype Monocytes/Macrophages determine for the most part the severity of the local inflammatory reaction to the corresponding irritant. With an IL-1-positive genotype, the monocytes are provoked to up to 4 times higher production of IL-1 by lipopolysaccharide (LPS) from gram-negative anaerobes (Pg, Tf, Td). Note: This local overproduction by hyperactive Mφ can be additionally elevated as a result of the autocrine (self-stimulating) effect of IL-1 (Deschner 2002).
430 Polymorphism—Genotype The chromosomes of tissue cells are present in two categories (diploid, one each from the mother and the father). Therefore in a SNP, three variants per gene are possible (A, B and C): A 2 times C (Cytosine: “normal”) = Allele 1 & 1, homozygote B 2 times T (Thymine; SNP) = Allele 2 & 2, homozygote C 1 time C and 1 time T = Alleles 1 & 2, heterozygote

Effect upon the Periodontium

The general effect of a positive IL-1 genotype is depicted in Figure 429.

Definition: The “IL-1-positive genotype” (“positive” with regard to SNP) is allocated to those individuals who possess the Allele 2 homozygote in one gene or at least heterozygosity in both IL genes (genes IL-1A and IL-1B; see above).

The elevated susceptibility to periodontal inflammation that is associated with the IL-positive genotype does not manifest itself immediately in the young persons, as long as no additional risk factors such as smoking, poor oral hygiene, systemic diseases such as diabetes mellitus (DM) etc. are present (Kornman et al. 1997). But if risks exist over a longer period of time, the IL-1 polymorphism accelerates and accentuates periodontitis to a great degree (“severity factor”; odds ratio ca. 1.5–2).

In difficult cases or in patients with high or multiple risk factors, the test for the existence of the IL-1 gene polymorphism is indicated.

IL-1 Gene Test—Technique, Evaluation

Today, periodontitis is categorized within the large group of multifactorial diseases. Therefore it is logical to seek out new test systems for the demonstration of genetic factors that could elevate susceptibility, progression or severity. Already recognized are polymorphisms of the genes or gene clusters of TNFα, IL-10 as well as receptors of T-cells, immunoglobulins (Fcγ-RII, -III etc.), cathepsin, vitamin D3 etc. Especially and most well-researched is the effect of a gene polymorphism upon periodontitis that can enhance the inflammatory process via interleukin 1 (IL-1α and β; Kornman et al. 1999).

Several specialized laboratories now offer interleukin-1 gene tests; all measure the SNP (“single nucleotide polymorphisms”) for the IL-1α; at locus +4845 or −889 (equal effects), for IL-1β at locus +3954.

These simple DNA tests require host cells, which can be taken from blood, saliva or from the oral buccal mucosa. The miniscule amount of DNA must be amplified using PCR (polymerase chain reaction; p. 183).

IL-1 gene-positive does not immediately indicate “severe periodontitis”: Its effect becomes critically important only in combination with additional risk co-factors.

431 IL-1 Gene Test–Harvest Technique Left: Using a sterile brush, the buccal mucosa is scraped to collect some epithelial cells for the molecular biological analysis. Right: The tip of the brush is inserted into a transport vial for the laboratory. IL-1 gene tests that are commercially available: PST—Interleukin Genetics GenoType PRT—Hain ParoGenTest—IAI Test Results: Consequences of a Positive IL-1 Gene Polymorphism
432 Case No. 1 At age 35, this patient exhibits 10% bone loss as a result of initial, chronic periodontitis. With very good oral hygiene and in the absence additional risk factors, 20 years later the 55-year-old individual will have retained all of the teeth; in areas that are naturally predisposed (molars, multi-rooted teeth etc.) bone loss may have advanced.
433 Case No. 2 In a patient of the same age and under the same conditions, but with only average oral hygiene, within 20 years one can expect pronounced bone loss and tooth loss. The positive IL-1 genotype functions primarily as a “severity factor”: It intensifies attachment loss and bone loss. Modified from the Hain Co. prospectus.

Risk Factor IL-1-positive Genotype—Additional Risk Factors

The genetic susceptibility–represented by the already described positive IL-1 genotype–does not, by itself, elicit periodontitis. The initiation and progression of this disease are, as heretofore, dependent upon bacteria, their pathogenicity and amount; therefore, the depth of the periodontal pockets also plays a major role (anaerobiosis!). The role that a positive IL-1 genotype might play was described by Socransky and coworkers (2000) for a primarily Caucasian population (Fig. 434): The association between positive genotype and severe, chronic periodontitis was observed only in older individuals (Fig. 433) and with deep pockets (Fig. 434). The positive genotype should therefore be viewed as a “severity factor.” It is noteworthy that the positive genotype (Allele 2; p. 189) was detected in only 8% of the examined Afro-Americans (Walker et al. 2000) and in only 2.3% of the examined Chinese patients (Armitage et al. 2000), but in every third Caucasian.

Additional important risks for periodontitis, alone or combined, are well acknowledged: Above all smoking and poor oral hygiene, then also systemic conditions (diabetes, HIV), and stress; there is a relationship also to patient age.

434 IL-1 Genotype–Pocket Depth and Bacterial Flora With a probing depth of 6 mm, the bacterial colonization is similar in IL-1 negative and IL-1 positive patients (diameter of the circles). In addition, the percentage composition of the various complexes does not vary significantly between the two cases. Beyond 6 mm probing depth, however, in an IL-1 positive patient one observes a dramatic alteration in terms of both the quantity of microorganisms as well as their quality (size of the circle; orange and red complexes). The strictly anaerobic milieu certainly plays an important role. The progression in the advanced stage of periodontitis appears to be greater/faster in patients who are genetically susceptible. The bacterial complexes that have been reported by Socransky et al. (1998) are depicted at the left in their various and most important groupings (p. 37, (Fig. 77). Modified from Socransky et al. 2000
435 More Risk Factors = Elevated Overall Risk Positive IL-1 Genotype in Combination with Additional Risk Factors In addition to the IL-1 positive genotype, three additional risk factors are portrayed. The individually more or less important factors (cf. odds ratios) become multiplied and as a result for the individual patient provide an estimate of the overall risk. This can be critical for therapy and long-term prognosis.
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Jul 2, 2020 | Posted by in Dental Hygiene | Comments Off on Tests of the Host Response—Risks
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