Sims Tom J, Lernmark Ake, Mancl Lloyd A, Schifferle Robert E, Page Roy C, Persson G Rutger
Department of Oral Medicine, University of Washington, Seattle WA 98195, USA.
J Clin Periodontol. 2002 Jun;29(6):551-62. doi: 10.1034/j.1600-051x.2002.290612.x.
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.
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.
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.
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).
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.
以往研究报道了牙周炎的存在及严重程度与牙龈卟啉单胞菌物种特异性抗原或交叉反应抗原（如脂多糖（LPS）和热休克蛋白（HSP），这些抗原在牙龈卟啉单胞菌和其他细菌中共有）的血清抗体滴度之间的相关性。我们最近对重度牙周炎的胰岛素依赖型（1型）糖尿病患者（IDDMI/牙周炎）的牙周治疗结果进行的研究得出了两个关键发现：1.血清谷氨酸脱羧酶自身抗体（GAD65 Ab）水平与牙周袋深度变化（PDC）显著相关；2.在血清阳性（GAD65 Ab +）患者中，针对牙龈卟啉单胞菌细胞的血清IgG滴度与GAD65 Ab水平呈正相关。因此，我们推测血清自身抗体水平和针对牙龈卟啉单胞菌特异性抗原的IgG滴度谱可能有助于评估此类患者难治性牙周炎的风险。
确定使用针对牙龈卟啉单胞菌特异性抗原、人HSP和GAD65的基线IgG滴度谱是否可以预测非手术牙周治疗导致的PDC。
对7例GAD65 Ab +和11例GAD65 Ab -的IDDMI/牙周炎患者进行非手术牙周治疗两个月后评估PDC。使用放射性配体沉淀或酶联免疫吸附（ELISA）测定法测量治疗前针对GAD65、重组人热休克蛋白（HSP90、HSP70和HSP60）以及各种牙龈卟啉单胞菌抗原的滴度，并与154例新发病的IDDMI患者和46例非糖尿病对照的相同测量结果进行比较。
GAD65 Ab +（p = 0.002）和GAD65 Ab -（p = 0.034）的IDDMI/牙周炎患者针对HSP90和HSP70的中位滴度（ELISA单位）分别显著高于非糖尿病对照。多变量回归分析表明PDC与HSP90（r = - 0.62，p = 0.008）、HSP70（r = + 0.62，p = 0.009）、GAD65（r = - 0.60，p = 0.01）和牙龈卟啉单胞菌LPS（r = - 0.51，p = 0.04）的对数转换滴度存在显著部分相关性。此外，对HSP90、HSP70和GAD65 Ab滴度的对数转换基线谱进行层次聚类，将患者分为两个不同的聚类，其PDC中位数显著不同（1.45分钟，n = 10对0.65分钟，n = 8；p = 0.016，曼-惠特尼检验）。
血清抗体滴度针对HSP90、HSP70、GAD65和牙龈卟啉单胞菌LPS的治疗前谱可能有助于预测哪些IDDMI/牙周炎患者对非手术牙周治疗反应不佳。
