Serum IgG to heat shock proteins and Porphyromonas gingivalis antigens in diabetic patients with periodontitis.
BACKGROUND
Past studies have reported a correlation between the presence and severity of periodontitis and serum antibody titers to species-specific antigens of Porphyromonas gingivalis or to cross-reactive antigens, such as lipopolysaccharide (LPS) and heat shock proteins (HSP), shared between P. gingivalis and other bacteria. Our recent study of periodontal treatment outcome in insulin-dependent (type 1) diabetes mellitus patients with severe periodontitis (IDDMI/periodontitis) resulted in two key findings: 1. serum glutamic acid decarboxylase autoantibody (GAD65 Ab) levels were significantly associated with periodontal pocket depth change (PDC) and 2. serum IgG titers to P. gingivalis cells were positively associated with GAD65 Ab level in seropositive (GAD65 Ab +) patients. We have therefore hypothesized that profiles of serum autoantibody levels and IgG titers, to P. gingivalis-specific antigens may be useful in assessing risk for refractory periodontitis in such patients.


OBJECTIVE
To determine whether PDC resulting from non-surgical periodontal treatment can be predicted using profiles of baseline IgG titers to P. gingivalis-specific antigens, human HSP, and GAD65.


METHODS
PDC was assessed two months after non-surgical periodontal treatment of 7 GAD65 Ab + and 11 GAD65 AbIDDM/periodontitis patients. Pretreatment titers to GAD65, recombinant human heat shock proteins (HSP90, HSP70, and HSP60), and various P. gingivalis antigens were measured using radioligand precipitation or enzyme-linked immunosorbent (ELISA) assays and compared to the same measurements for 154 recent-onset IDDM patients and 46 non-diabetic controls.


RESULTS
Median titers (ELISA units) to HSP90 and HSP70 were significantly higher than non-diabetic controls for GAD65 Ab + (p degrees = 0.002) and GAD65 Ab- (p = 0.034) IDDM/periodontitis patients, respectively. Multivariate regression analysis indicated significant partial correlation of PDC with log-transformed titers to HSP90 (r = - 0.62, p = 0.008), HSP70 (r = + 0.62, p = 0.009), GAD65 (r = - 0.60, p = 0.01) and P. gingivalis LPS (r = - 0.5 1, p = 0.04). Furthermore, hierarchical clustering of baseline profiles of log-transformed HSP90, HSP70, and GAD65 Ab titers sorted patients into two distinct clusters with significantly different median PDC (1.45 min, n = 10 vs. 0.65 min, n = 8; p = 0.016, Mann-Whitney).


CONCLUSIONS
Pretreatment profiles of serum antibody titers to HSP90, HSP70, GAD65, and P. gingivalis LPS may be useful for predicting which patients with IDDM/periodontitis will have a poor response to non-surgical periodontal therapy.
Sims
Tom J
TJ
Department of Oral Medicine, University of Washington, Seattle WA 98195, USA. tomsims@u.washington.edu
Lernmark
Ake
A
Mancl
Lloyd A
LA
Schifferle
Robert E
RE
Page
Roy C
RC
Persson
G Rutger
GR
D000907:Antibodies, Bacterial / Q000276:immunology; D000942:Antigens, Bacterial / Q000276:immunology*; D001323:Autoantibodies / Q000097:blood; D018834:Chaperonin 60 / Q000276:immunology; D003922:Diabetes Mellitus, Type 1 / Q000097:blood / Q000276:immunology*; D004797:Enzyme-Linked Immunosorbent Assay; D005500:Follow-Up Studies; D005968:Glutamate Decarboxylase / Q000276:immunology; D018840:HSP70 Heat-Shock Proteins / Q000276:immunology; D018841:HSP90 Heat-Shock Proteins / Q000276:immunology; D006360:Heat-Shock Proteins / Q000276:immunology*; D006801:Humans; D007074:Immunoglobulin G / Q000097:blood*; D007527:Isoenzymes / Q000276:immunology; D016014:Linear Models; D008070:Lipopolysaccharides / Q000276:immunology; D015999:Multivariate Analysis; D010514:Periodontal Pocket / Q000276:immunology; D010518:Periodontitis / Q000097:blood / Q000276:immunology* / Q000628:therapy; D016966:Porphyromonas gingivalis / Q000276:immunology*; D012008:Recurrence; D012044:Regression Analysis; D018570:Risk Assessment; D018709:Statistics, Nonparametric
D000907:Antibodies, Bacterial; D000942:Antigens, Bacterial; D001323:Autoantibodies; D018834:Chaperonin 60; D018840:HSP70 Heat-Shock Proteins; D018841:HSP90 Heat-Shock Proteins; D006360:Heat-Shock Proteins; D007074:Immunoglobulin G; D007527:Isoenzymes; D008070:Lipopolysaccharides; D005968:Glutamate Decarboxylase; C401141:glutamate decarboxylase 2