Bioreactivity Markers in Total Hip Replacments

描述(由申请者提供)：本项目涉及 全髋关节降解产物的免疫反应性现象 关节成形术(THA)组件导致骨丢失和种植失败。这 提案的重点是离子和颗粒生物材料诱导的细胞 THA患者淋巴细胞和单核/巨噬细胞的反应它 继续观察临床部分患者全关节 关节成形术可耐受微粒负荷和金属蛋白复合体 形成时间较长(&gt；8年)，但相对较少 种植体周围的反应性，而其他患者似乎相同 颗粒和离子负荷显示出明显的反应性，在2-7 数年，导致种植体周围骨吸收。免疫系统的细胞 主要调解这些事件。巨噬细胞吞噬的颗粒和 金属-蛋白质复合体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的因素 要么增加骨吸收，要么减少骨形成。在我们的 初步的工作表明，1)分解代谢的标志物改变 2)部分患者的淋巴细胞在THA后升高。 对某些金属盐的高反应性；以及3)患者的单核细胞 THA处于致敏状态并产生更多的细胞因子和 与单核细胞相比，二十烷基类化合物对颗粒碎片的反应更强 从正常人身上分离出来。我们假设免疫的血清标记物 易患THA患者的反应性和胶原分解代谢升高 骨溶解和无菌性松动以及离子(金属-蛋白质复合体)和 微粒植入碎片在不同的环境中产生不同程度的反应 个体，部分是通过免疫细胞的可变激活 系统。我们建议通过将血清和尿液联系起来来检验这些假设。 炎症和胶原分解代谢的标志物与血管病变的关系 有和不有人工全髋关节置换术患者中特征良好的骨溶解 在单个时间点进行骨溶解(AI-A4组)，然后使用这些 在发育前确定了指示骨溶解开始的标志物 每年收集的临床症状和/或放射学变化 前瞻性跟踪队列患者的血清和尿液(组 131-134)。此外，植入物诱导的不同免疫反应 降解产物(即淋巴细胞对金属离子的反应和 单核/巨噬细胞对颗粒碎片的反应)将与 骨溶解的研究进展

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