Bioreactivity Markers in Total Hip Replacments

描述（由申请人提供）：该项目涉及 全髋关节降解产物免疫反应现象 关节成形术（THA）部件导致骨丢失和植入物失效。这 建议侧重于离子和颗粒生物材料诱导的细胞 THA患者淋巴细胞和单核细胞/巨噬细胞的反应。它 临床上继续观察到，一些全关节患者 关节成形术可以耐受颗粒负荷和金属蛋白复合物 长期形成（>8年）， 植入物周围反应，而其他患者似乎等同 颗粒和离子负荷在2-7 年，导致种植体周围骨吸收。免疫系统的细胞 主要负责这些事件的调解。被巨噬细胞吞噬的颗粒， 金属-蛋白质复合物与淋巴细胞相互作用可导致产生 以自分泌和旁分泌的方式起作用， 增加骨吸收或减少骨形成。在我们 初步研究表明，1）分解代谢骨变化的标志物 THA后升高; 2）来自选定THA患者的淋巴细胞， 对某些金属盐的高反应性;和3）来自患有 THA处于致敏状态，产生大量细胞因子， 与单核细胞相比，类花生酸对颗粒碎片激发的响应 与正常人隔离。我们假设免疫系统的血清标志物 THA患者的反应性和胶原蛋白水平升高， 骨质溶解和无菌性松动，以及离子（金属-蛋白质复合物）和 颗粒植入物碎片在不同的组织中产生不同水平的反应性， 个体，部分通过免疫细胞的可变激活， 系统我们建议通过血清和尿液的相关性来检验这些假设 炎症和胶原蛋白分解代谢的标志物 在一个充分表征的THA患者队列中， 在单个时间点（A1-A4组）观察骨质溶解，然后使用这些 在发生骨质溶解之前，确定了指示骨质溶解发生的标志物 临床症状和/或影像学变化， 前瞻性随访患者队列的血清和尿液（组 131-134）。此外，植入物诱导的可变免疫应答 降解产物（即淋巴细胞对金属离子的反应， 单核细胞/巨噬细胞对颗粒碎片的反应）将与 骨质溶解的发展

DESCRIPTION (provided by applicant): This project is concerned with the phenomenon of immunologic reactivity to degradation products of total hip arthroplasty (THA) components leading to bone loss and implant failure. This proposal focuses on ionic and particulate biomaterial-induced cellular responses of lymphocytes and monocytes/macrophages in patients with THA. It continues to be observed clinically that some patients with total joint arthroplasties can tolerate particulate burden and metal-protein complex formation for long periods of time (>8 years) with relatively little peri-implant reactivity, whereas other patients with seemingly equivalent particulate and ionic burdens demonstrate pronounced reactivity within 2-7 years, resulting in peri-implant bone resorption. Cells of the immune system primarily mediate these events. Particles phagocytosed by macrophages and metal-protein complexes interacting with lymphocytes can lead to the production of factors which act in both an autocrine and paracrine fashion and contribute to either increased bone resorption or reduced bone formation. In our preliminary work, it has been shown that 1) markers of catabolic bone changes are elevated after THA; 2) lymphocytes from selected patients with THA are hyper-responsive to certain metal salts; and 3) monocytes from patients with THA are in a sensitized state and produce larger amounts of cytokines and eicosanoids in response to challenge with particulate debris than monocytes isolated from normal individuals. We hypothesize that serum markers of immune reactivity and collagen catabolism are elevated in THA patients prone to osteolysis and aseptic loosening and that ionic (metal-protein complexes) and particulate implant debris produce diverse levels of reactivity in different individuals, in part, through variable activation of cells of the immune system. We propose to test these hypotheses by correlating serum and urine markers of inflammation and Collagen catabolism with the development of osteolysis in a wellcharacterized cohort of THA patients with and without osteolysis at a single time point (Groups AI-A4), and then to use these identified markers to indicate the onset of osteolysis prior to the development of clinical symptoms and/or radiographic changes within the annually collected serum and urine of a prospectively followed cohort of patients (Groups 131-134). Additionally, variable immunologic responses induced by implant degradation products (i.e. lymphocyte response to metal ions and monocyte/macrophage response to particulate debris) will be correlated with the development of osteolysis