Peridontal infection, antiphospholipids & Prematurity

牙周感染，抗磷脂

• 批准号: 7620861
• 负责人: Harvey Schenkein
• 金额: $ 19.3万
• 依托单位: VIRGINIA COMMONWEALTH UNIVERSITY
• 依托单位国家: 美国
• 资助国家: 美国
• 起止时间: 至
• 项目状态: 未结题
• 来源: https://reporter.nih.gov/project-details/7620861
• 关键词: Accounting; Address; African American; Antibodies; Anticardiolipin Antibodies; Antigen-Antibody Complex; Antiphospholipid Antibodies; Antiphospholipid Syndrome; Autoimmune Diseases; Biological Process; Birth; Birth Weight; Cardiolipins; Chronic; Complex; Condition; Dendritic Cells; Exhibits; Fetal Growth Retardation; Fetus; Functional disorder; Glycoproteins; Growth; Health; Immune; Immunologic Factors; Individual; Infection; Lead; Link; Low Birth Weight Infant; Low-Density Lipoproteins; Lymphocyte; Minimally modified Low Density Lipoprotein; Minority; Modeling; Molecular Mimicry; Mothers; Mus; Pathogenicity; Patients; Periodontal Diseases; Periodontal Infection; Periodontitis; Placenta; Placental Insufficiency; Population; Porphyromonas gingivalis; Pregnancy; Pregnancy Outcome; Premature Birth; Premature Infant; Premature Labor; Prematurity of fetus; Production; Property; Race; Rate; Reaction; Research; Risk; Risk Factors; Severities; Spontaneous abortion; Time; Woman; cytokine; fetal; interest; mouse model; oral infection; oral pathogen; prototype; vasoconstriction; Accounting; Address; African American; Antibodies; Anticardiolipin Antibodies; Antigen-Antibody Complex; Antiphospholipid Antibodies; Antiphospholipid Syndrome; Autoimmune Diseases; Biological Process; Birth; Birth Weight; Cardiolipins; Chronic; Complex; Condition; Dendritic Cells; Exhibits; Fetal Growth Retardation; Fetus; Functional disorder; Glycoproteins; Growth; Health; Immune; Immunologic Factors; Individual; Infection; Lead; Link; Low Birth Weight Infant; Low-Density Lipoproteins; Lymphocyte; Minimally modified Low Density Lipoprotein; Minority; Modeling; Molecular Mimicry; Mothers; Mus; Pathogenicity; Patients; Periodontal Diseases; Periodontal Infection; Periodontitis; Placenta; Placental Insufficiency; Population; Porphyromonas gingivalis; Pregnancy; Pregnancy Outcome; Premature Birth; Premature Infant; Premature Labor; Prematurity of fetus; Production; Property; Race; Rate; Reaction; Research; Risk; Risk Factors; Severities; Spontaneous abortion; Time; Woman; cytokine; fetal; interest; mouse model; oral infection; oral pathogen; prototype; vasoconstriction

Premature birth is a national health crisis occurring at a rate approximating 12%. Recent research has demonstrated that maternal periodontal disease is a risk factor for both premature birth and low birth weight. Importantly, individuals in minority populations, and particularly African Americans, are at increased risk for both premature birth and periodontal diseases. We have previously demontrated that subset of periodontitis patients exhibit elevated levels of the antiphospholipid antibody anticardiolipin (anti-CL). These antibodies have been linked with miscarriages and premature birth. In a preliminary retrospective analysis of birth weight and gestation of babies born to women who were later identified to have periodontal disease, we found strong associations between maternal levels of anti-CL and both birth weight and prematurity. However, this observation requires further study because the average time between the births and the periodontal examinations and antibody determinations was nearly 10 years. Placental proinflammatory cytokines are found to be dominant in placenta! insufficient-growth restricted fetuses, and we have additionally observed that anti-CL was able to form immune complexes with both oral pathogens and minimally-modified LDL. When these complexes interacted with dendritic cells (DCs), production of proinflammatory cytokines (IL-12p70 and IFN-y) by both DC and stimulated lymphocytes was enhanced. Thus, both the procoagulant and proinflammatory properties of antiphospholipids may contribute to increased risk for preterm birth observed in mothers with periodontal infections. We therefore hypothesize that periodontitis contributes to the occurrence of placental insufficiency that leads to restricted growth and premature birth due to induction of anti-CL by the periodontal microflora. We propose to address this hypothesis by determining the association of periodontitis and anti-CL with the severity of fetal growth restriction in 400 women with premature labor. We will further characterize the immunohistopathological changes in the placenta and cytokine profiles that might account for the occurrence of fetal growth restriction. Furthermore, we will assess the pathogenicity of anti-CL from mothers with periodontitis in a mouse pregnancy model, and examine the ability of P. gingivalis to induce such antibody. These studies address a previously unstudied mechanism linking chronic oral infection and fetal growth restriction.

过早出生是发生的国家健康危机，速度约为12％。最近的研究已有 证明产妇牙周疾病是早产和低出生体重的危险因素。 重要的是，少数民族，尤其是非裔美国人的个人有增加的风险 早产和牙周疾病。我们以前已经对牙周炎的子集进行了控制 患者表现出抗磷脂抗体抗生素（抗CL）的水平升高。这些抗体 与流产和早产有关。在初步回顾性分析中 妇女出生的婴儿的体重和妊娠，后来被确定患有牙周疾病，我们 发现抗CL的产妇水平与出生体重和早产之间有着密切的关联。 但是，这一观察结果需要进一步研究，因为分娩和 牙周检查和抗体测定近10年。胎盘促炎 发现细胞因子在胎盘中占主导地位！增长限制不足的胎儿，我们有 此外，观察到抗CL能够与两种口腔病原体和 最小化的LDL。当这些复合物与树突状细胞（DC）相互作用时 DC和刺激的淋巴细胞都增强了促炎细胞因子（IL-12P70和IFN-Y）。 因此，抗磷脂的pro凝和促炎特性都可能有助于 患有牙周感染的母亲观察到的早产风险增加。因此，我们假设 牙周炎导致胎盘不足的发生，从而导致限制生长和 由于牙周菌群诱导抗CL而导致的过早出生。我们建议解决这个问题 通过确定牙周炎和抗CL与胎儿生长严重程度的关联来假设 400名劳动过早妇女的限制。我们将进一步表征免疫组织病理学 胎盘和细胞因子特征的变化可能解释了胎儿生长的发生 限制。此外，我们将评估A中患有牙周炎母亲的抗CL的致病性 小鼠妊娠模型，并检查牙龈疟原虫诱导这种抗体的能力。这些研究 处理以前未研究的机制，将慢性口腔感染和胎儿生长限制联系起来。