Association of natural anti-platelet factor 4/heparin antibodies with periodontal disease
Association of natural anti-platelet factor 4/heparin antibodies with periodontal disease
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DOI：
10.1182/blood-2011-03-342857
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发表时间：
2011-08-04
期刊：
影响因子：
20.3
通讯作者：
Kocher, Thomas
中科院分区：
文献类型：
--
作者：
Greinacher, Andreas;Holtfreter, Birte;Kocher, Thomas
血小板因子4（PF 4）和肝素（H）形成PF 4/H复合物，是肝素诱导的血小板减少症（HIT）中免疫反应的靶点。HIT似乎是一种二次免疫应答，因为抗PF 4/H-IgG抗体早在肝素治疗第4天就出现。本研究调查了流行性感染如牙周炎是否可以诱导PF 4/H免疫应答，因为：（1）正常人群中存在天然抗PF 4/H抗体;（2）与细菌结合的PF 4暴露与PF 4/H复合物相同的抗原;（3）脓毒症诱导小鼠中的PF 4/H抗体。我们发现PF 4结合牙周病原体（Aggregatibacteractinomycetemcomitans;牙龈卟啉单胞菌），使随后的人抗PF 4/H抗体的结合。在病例对照研究中评估了天然PF 4/HAb与牙周炎的相关性，招募了天然抗PF 4/HAb的个体（n = 40对配对），并在波美拉尼亚健康的横断面人群研究（SHIP; n = 3500）中进行了评估。两项研究均显示牙周炎与抗PF 4/H抗体的存在之间存在强相关性，与炎症标志物无关（病例对照研究：最低与最高三分位数，比值比，7.12 [95%置信区间，1.73-46.13; P = .005]; SHIP研究，p（趋势）
Platelet factor 4 (PF4) and heparin (H) form PF4/H complexes, the target of the immune reaction in heparin-induced thrombocytopenia (HIT). HIT seems to be a secondary immune response as anti-PF4/H-IgG antibodies occur as early as day 4 of heparin treatment. This study investigated whether prevalent infections such as periodontitis may induce the PF4/H immune response as: (1) natural anti-PF4/H Abs are present in the normal population; (2) PF4 bound to bacteria exposes the same antigen(s) as PF4/H complexes; and (3) sepsis induces PF4/H Abs in mice. We found PF4 bound to periodontal pathogens (Aggregatibacter actinomycetemcomitans; Porphyromonas gingivalis) enabling subsequent binding of human anti-PF4/H Abs. The association of natural PF4/HAbs and periodontitis was assessed in a case-control study, enrolling individuals with natural antiPF4/H Abs (n = 40 matched pairs), and in the cross-sectional population-based Study of Health in Pomerania (SHIP; n = 3500). Both studies showed a robust association between periodontitis and presence of anti-PF4/H Abs independent of inflammation markers (case-control study: lowest vs highest tertile, odds ratio, 7.12 [95% confidence interval, 1.73-46.13; P = .005]; SHIP study, p(trend)