Resumen de Serum Antibody Responses to Periodontal Microbiota in Chronic and Aggressive Periodontitis: A Postulate Revisited
Background: The authors revisited the 1999 International Workshop postulate of robust serum antibody responses to infecting agents in localized aggressive periodontitis (LAgP) and weak responses in generalized aggressive periodontitis (GAgP). Antibody responses were further examined in localized and generalized chronic periodontitis (LCP and GCP).
Methods: The study includes 119 patients (60 males and 59 females, aged 11 to 76 years), 18 with LAgP, 37 with GAgP, 37 with LCP, and 27 with GCP. Multiple subgingival plaque samples/patient (1,057 in total) were analyzed with respect to 11 bacterial species using checkerboard DNA-DNA hybridizations, and serum immunoglobulin (Ig)G levels were measured against the same bacteria using checkerboard immunoblotting. Further, infection ratios (antibody level over the average bacterial colonization by the homologous species) were computed for each patient. Comparisons of bacterial colonization, serum IgG levels, and infection ratios were made across the diagnostic categories using multivariable linear regression models adjusting for age and race/ethnicity.
Results: There were no statistically significant differences in serum IgG levels to Aggregatibacter actinomycetemcomitans among the four diagnostic categories. IgG levels to several species, including Porphyromonas gingivalis, Treponema denticola, and Campylobacter rectus, were highest in patients with GAgP and significantly different from LCP and GCP, but not from LAgP. Comparisons based on infection ratios showed no statistically significant differences for any species between GAgP and LAgP.
Conclusion: This study provides evidence against the 1999 Workshop�s postulate of weak serum antibody responses in patients with GAgP and shows that serum IgG responses in GAgP are comparable to those in LAgP, but higher than in GCP or LCP for several species.
The diagnostic utility of serum antibody levels to periodontal microbiota in the identification and classification of periodontitis is rather poorly substantiated in the literature. Periodontitis is widely recognized as a bacterially driven inflammatory disease,1 and antibody responses to several periodontal microbiota are indeed detectable in the sera of patients with periodontitis.2 Presence of a systemic antibody response is thought to reflect the involvement of particular microbial species in the disease process and has been deemed important in the identification of periodontal pathogens.1 Yet, antibody titers to periodontal bacteria have not been convincingly established as valuable diagnostic aids. Although patients with periodontitis generally display higher levels of serum antibacterial immunoglobulin (Ig)G antibodies than periodontally healthy controls,3-6 periodontitis-free individuals also exhibit serum antibody responses to periodontal pathogens,5-7 albeit at lower levels. The authors have earlier assessed serum IgG levels to 19 periodontal bacteria in a nationally representative population sample8 and reported that a combination of specific titers, along with demographic and behavioral characteristics, can be used as a surrogate for clinical periodontal status in epidemiologic studies. However, the accuracy of this serology-based classification was rather modest.8 The authors subsequently demonstrated that: 1) edentulous individuals show lower antibody responses than dentate participants, notably against red complex species and Aggregatibacter actinomycetemcomitans, and 2) age, race/ethnicity, and current smoking status are important determinants of serum antibody levels.9 The consensus report of the 1999 International Workshop for the Classification of Periodontal Diseases and Conditions10 states that patients with localized aggressive periodontitis (LAgP) show robust antibody responses to infecting agents, while in contrast, patients with generalized aggressive periodontitis (GAgP) show poor systemic antibody responses. This conclusion was founded on the notion that serum antibody responses to periodontal microbiota have a largely protective role,11,12 and thus, development of severe, generalized periodontitis, especially at a young age, signified a likely impairment in adaptive immunity.13 However, a distinction between the two principal diagnostic categories of periodontitis (chronic and aggressive) based on the intensity of serum antibody responses to periodontal microbiota has not been well documented in the literature. In addition, it must be realized that these postulates on different antibody responses between LAgP and GAgP primarily stem from observations in patients diagnosed with either localized or generalized juvenile periodontitis, i.e., individuals under the age of 30 years. Thus, these conclusions may not be applicable to the diagnosis of aggressive periodontitis as defined in the 1999 Workshop, which encompasses individuals of all ages. Furthermore, the studies underlying these postulates were primarily focused on antibody responses to A. actinomycetemcomitans and, to a lesser extent, Porphyromonas gingivalis; therefore, the broader statement of weak antibody responses to �infecting agents� in general is poorly justified. Finally, the issue of �weak� versus �robust� responses has been addressed on the basis of serum antibody levels solely, without any accounting for the actual periodontal bacterial load. Concomitant adjustment for colonization levels appears to be particularly important given the recent findings by Pussinen et al.,14 who demonstrated that bacterial carriage is the strongest determinant of the level of systemic antibody responses to periodontal pathogens. In an earlier study, the present authors tested the above postulates and could not document any appreciable differences in serum antibody responses between LAgP and GAgP, as well as between chronic and aggressive periodontitis.15 In that study, the authors introduced the concept of �infection ratio,� defined as the ratio of an individual�s serum IgG antibody level to a given periodontal microbe to the same person�s average bacterial colonization by the homologous species, computed across multiple subgingival plaque samples. The authors argued that infection ratios better reflect a measure of �host responsiveness� to the aggregate periodontal bacterial burden than serum antibody levels alone. Nevertheless, limitations of that study included a relatively small sample size (57 individuals), a skewed sex distribution (25% male), and a lack of adjustments for age and race/ethnicity.
In the present study, the authors reexamine the issue of responsiveness to periodontal microbiota in chronic and aggressive periodontitis and their extent-based subdivisions (localized/generalized), using a larger sample of well-phenotyped patients and after adjusting for important covariates such as age, sex, and race/ethnicity that were earlier shown to affect serum antibody levels.9
