Heterogeneity of host immunological risk factors in patients with aggressive periodontitis.
BACKGROUND
The pathogenesis of early-onset periodontitis (EOP) can be explained by various host risk factors. Previous studies have focused on a single (among many possible) immunological risk factor and the association among the factors has not been assessed. We comprehensively investigated the associations among multiple host immunological risk factors in EOP patients to further elucidate their role in the pathogenesis of EOP.


METHODS
Sixty-eight EOP patients (50 generalized EOP, 18 localized EOP), 51 EOP-suspected patients (S-EOP), 43 adult periodontitis (AP) patients, and 36 periodontally healthy subjects (HS) participated in this cross-sectional study. We examined peripheral neutrophil functions, phenotypic and functional characterization of peripheral lymphocytes (lymphocyte subsets, T-cell proliferative activity), cytokine productivity (interleukin [IL]-1, IL-2, tumor necrosis factor [TNF]-alpha, interferon [IFN]-gamma, IL-4 and IL-6), serum immunoglobulin G (IgG) antibody titers against 12 periodontal bacteria, and HLA class II genotypes.


RESULTS
G-EOP, S-EOP, and AP patient groups showed significantly lower percentages of pan T cells and CD8-positive cells (P < 0.02) compared with the HS group. L-EOP patients showed depressed IL-4 and TNF-alpha productivity compared with the HS group (P < 0.02). The EOP group showed significantly elevated antibody levels against Actinobacillus actinomycetemcomitans, Porphyromonas gingivalis, Treponema denticola, and Fusobacterium nucleatum compared with the HS group (P < 0.05). The frequency with DQB1*0503 was significantly higher in the EOP patient group than the HS group (P = 0.045) due to the higher frequency in L-EOP patients than the HS group (P = 0.035). There were wide interindividual variations in each of the tests among patient and HS groups; however, EOP patients showed wider intradiagnostic group variations in certain host defensive cell functions than the other groups. There were some EOP patients who showed extremely low or high values in some tests; the EOP patients could be further divided into subgroups according to their host defensive and immunological profiles. However, there was heterogeneity in some of the other host immunological tests even in the subgroups.


CONCLUSIONS
The association of host immunological risk factors in EOP patients is widely varied and more complex than previously thought. These results indicate the difficulty of explaining the pathogenesis of EOP based on a single host risk factor and also emphasize the importance of critical assessment of not only EOP patient groups, but also individual patients.
Takahashi
K
K
Department of Periodontology and Endodontology, Okayama University Dental School, Okayama, Japan.
Ohyama
H
H
Kitanaka
M
M
Sawa
T
T
Mineshiba
J
J
Nishimura
F
F
Arai
H
H
Takashiba
S
S
Murayama
Y
Y
D000328:Adult; D016976:Aggregatibacter actinomycetemcomitans / Q000276:immunology; D010520:Aggressive Periodontitis / Q000276:immunology*; D000907:Antibodies, Bacterial / Q000097:blood; D018414:CD8-Positive T-Lymphocytes / Q000276:immunology; D003430:Cross-Sectional Studies; D005260:Female; D016967:Fusobacterium nucleatum / Q000276:immunology; D005838:Genotype; D006683:HLA-DQ Antigens / Q000235:genetics; D059866:HLA-DQ beta-Chains; D000949:Histocompatibility Antigens Class II / Q000235:genetics; D006801:Humans; D007074:Immunoglobulin G / Q000097:blood; D007371:Interferon-gamma / Q000276:immunology; D007375:Interleukin-1 / Q000276:immunology; D007376:Interleukin-2 / Q000276:immunology; D015847:Interleukin-4 / Q000276:immunology; D015850:Interleukin-6 / Q000276:immunology; D016131:Lymphocyte Subsets / Q000276:immunology; D008297:Male; D008875:Middle Aged; D009504:Neutrophils / Q000276:immunology; D010518:Periodontitis / Q000276:immunology*; D016966:Porphyromonas gingivalis / Q000276:immunology; D012307:Risk Factors; D013223:Statistics as Topic; D018709:Statistics, Nonparametric; D013601:T-Lymphocytes / Q000276:immunology; D014208:Treponema / Q000276:immunology; D014409:Tumor Necrosis Factor-alpha / Q000276:immunology
D000907:Antibodies, Bacterial; D006683:HLA-DQ Antigens; D059866:HLA-DQ beta-Chains; C069051:HLA-DQB1 antigen; D000949:Histocompatibility Antigens Class II; D007074:Immunoglobulin G; D007375:Interleukin-1; D007376:Interleukin-2; D015850:Interleukin-6; D014409:Tumor Necrosis Factor-alpha; D015847:Interleukin-4; D007371:Interferon-gamma