Tests of the Host Response—Risks
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.
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.
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.
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.