ABSTRACT Chronic periodontitis (CP) is a chronic inflammatory condition which destroys the supporting tissues of teeth and increases in prevalence with age. Immune responses against heat shock proteins (HSP) can be cross-reactive among bacterial and human antigens. There is evidence that microbial HSP65 and human HSP60 are involved in periodontal disease. The aim of this study is to investigate immune responses to the human HSP60 and microbial HSP65 in patients with CP and relate these to the level of inflammation and smoking status. We collected serum samples from 30 patients with chronic gingivitis (CG) and 30 patients with CP. In each group, eight subjects were current smokers. ELISA was used to determine the levels of serum anti-HSP and C-reactive protein (CRP) in each group. Peripheral blood mononuclear cells were also isolated and stimulated with HSPs. Significant lymphoproliferation was seen in CP when stimulated with human HSP60. CRP and serum anti-human HSP60 IgG were elevated in CP compared to the CG, but not serum anti-microbial HSP 65 IgG. In view of the potential confounding effects of smoking in CP, a group of current smokers (n = 16) was also recruited to investigate whether smoking affects HSP immune responses. There was no significant difference in HSP-induced lymphoproliferation between smokers and non-smokers in either the CG or CP. There was a significant correlation between CRP and lymphoproliferative responses to Human HSP60 irrespective of smoking status. This study shows that serum anti-human HSP60 IgG and serum CRP are raised in untreated CP. In CP, serum CRP levels correlated significantly with human HSP60-induced lymphoproliferation, but not with anti-HSP antibody levels.
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A. Hasan, M. Foo, D. Sadoh and B. Jones, "Immune Responses to HSP65/60 in Periodontal Disease," Journal of Immune Based Therapies, Vaccines and Antimicrobials, Vol. 1 No. 2, 2012, pp. 7-13. doi: 10.4236/jibtva.2012.12002.
 D. Locker, G. D. Slade and H. Murray, “Epidemiology of Periodontal Disease among Older Adults: A Review,” Periodontology 2000, Vol. 16, No. 1, 1998, pp. 16-33.
M. A. Listgarten and P. M. Loomer, “Microbial Identification in the Management of Periodontal Diseases. A Systematic Review,” Annals of Periodontology, Vol. 8, No. 1, 2003, pp. 182-192.
P. S. Kumar, et al., “New Bacterial Species Associated with Chronic Periodontitis,” Journal of Dental Research, Vol. 82, No. 5, 2003, pp. 338-344.
S. Amar, et al., “Periodontal Disease Is Associated With Brachial Artery Endothelial Dysfunction and Systemic Inflammation,” Arteriosclerosis, Thrombosis, and Vascular Biology, Vol. 23, No. 7, 2003, pp. 1245-1249.
K. Buhlin, et al., “Risk Factors for Cardiovascular Disease in Patients with Periodontitis,” European Heart Journal, Vol. 24, No. 23, 2003, pp. 2099-2107.
S. Jindal, et al., “Primary Structure of a Human Mitochondrial Protein Homologous to the Bacterial and Plant Chaperonins and to the 65-Kilodalton Mycobacterial Antigen,” Molecular and Cellular Biology, Vol. 9, No. 5, 1989, pp. 2279-2283.
J. E. R. Thole, et al., “Antigenic Relatedness of a Strongly Immunogenic 65 kDA Mycobacterial Protein Antigen with a Similarly Sized Ubiquitous Bacterial Common Antigen,” Microbial Pathogenesis, Vol. 4, No. 1, 1988, pp. 71-83.
A.Hasan, et al., “The immune responses to human and microbial heat shock proteins in periodontal disease with and without coronary heart disease,” Clinical & Experimental Immunology, Vol. 142, No. 3, 2005, pp. 585-594.
D. E. Lopatin, et al. “Humoral Immunity to Stress Proteins and Periodontal Disease,” Journal of Periodontology, Vol. 70, No. 10, 1999, pp. 1185-1193.
K. Tabeta, et al., “Elevated Humoral Immune Response to Heat Shock Protein 60 (hsp60) Family in Periodontitis Patients,” Clinical & Experimental Immunology, Vol. 120, No. 2, 2000, pp. 285-293.
G. Schett, et al., “Salivary Anti-hsp65 Antibodies as a Diagnostic Marker for Gingivitis and a Possible Link to Atherosclerosis,” International Archives of Allergy and Immunology, Vol. 114, No. 3, 1997, pp. 246-250.
H. Direskeneli, et al., “Recognition of B-Cell Epitopes of the 65 kDa HSP in Beh?et’s Disease,” Scandinavian Journal of Immunology, Vol. 43, No. 4, 1996, pp. 464- 471. doi:10.1046/j.1365-3083.1996.d01-53.x
K. Pervin, et al., “T Cell Epitope Expression of Mycobacterial and Homologous Human 65-Kilodalton Heat Shock Protein Peptides in Short Term Cell Lines from Patients with Behcet’s Disease,” The Journal of Immunology, Vol. 151, No. 4, 1993, pp. 2273-2282.
R. R. Ranney, “Classification of Periodontal Diseases,” Periodontology 2000,” Vol. 2, No. 1, 1993, pp. 13-25.
J. C. Gunsolley, et al., “Serum antibodies to periodontal bacteria,” Journal of Periodontology, Vol. 61, No. 7, 1990, pp. 412-419. doi:10.1902/jop.1922.214.171.1242
K. Yamazaki, et al., “Effect of Periodontal Treatment on the Serum Antibody Levels to Heat Shock Proteins,” Clinical & Experimental Immunology, Vol. 135, No. 3, 2004, pp. 478-482.
R. Genco, S. Offenbacher and J. Beck, “Periodontal Disease and Cardiovascular Disease,” The Journal of the American Dental Association, Vol. 133, 2002, pp. 14S- 22S.
P. P. Hujoel, et al., “Periodontal Disease and Coronary Heart Disease Risk,” The Journal of the American Medical Association, Vol. 284, No. 11, 2000, pp. 1406-1410.
R. M. Palmer, et al., “Potential Mechanisms of Susceptibility to Periodontitis in Tobacco Smokers,” Journal of Periodontal Research, Vol. 34, No. 7, 1999, pp. 363-369.
M. I. Ryder, et al., “Effects of Tobacco Smoke on the Secretion of Interleukin-1β, Tumor Necrosis Factor-α, and Transforming Growth Factor-β from Peripheral Blood Mononuclear Cells,” Oral Microbiology and Immunology, Vol. 17, No. 6, 2002, pp. 331-336.
E. Yamaguchi, et al., “Release of Tumor Necrosis Factor-Alpha from Human Alveolar Macrophages is Decreased in Smokers,” Chest, Vol. 103, No. 2, 1993, pp. 479-483. doi:10.1378/chest.103.2.479.
M. Ide, et al., “Effect of Treatment of Chronic Periodontitis on Levels of Serum Markers of Acute-Phase Inflammatory and Vascular Responses,” Journal of Clinical Periodontology, Vol. 30, No. 4, 2003, pp. 334-340.
F. D’Aiuto, et al., “Periodontitis and Systemic Inflammation: Control of the Local Infection is Associated with a Reduction in Serum Inflammatory Markers,” Journal of Dental Research, Vol. 83, No. 2, 2004, pp. 156-160.
A. Veres, et al., “Relationship of Anti-60 kDa Heat Shock Protein and Anti-Cholesterol Antibodies to Cardiovascular Events,” Circulation, Vol. 106, No. 22, 2002, pp. 2775-2780.
J. Zhu, et al., “Antibodies to Human Heat-Shock Protein 60 Are Associated With the Presence and Severity of Coronary Artery Disease: Evidence for an Autoimmune Component of Atherogenesis,” Circulation, Vol. 103, No. 8, 2001, pp. 1071-1075. doi:10.1161/01.CIR.103.8.1071
K. Yamazaki, et al., “Accumulation of Human Heat Shock Protein 60-Reactive T Cells in the Gingival Tissues of Periodontitis Patients,” Infection and Immunity, Vol. 70, No. 5, 2002, pp. 2492-2501.
M. D. A. Petit, et al., “Depressed Responsiveness of Pe-ripheral Blood Mononuclear Cells to Heat-shock Proteins in Periodontitis Patients,” Journal of Dental Research, Vol. 78, No. 8, 1999, pp. 1393-1400.