Clinic of Orthopedics and Sports Orthopedics, Klinikum rechts der Isar, Technische Universität München, Ismaninger Straβe 22, 81675 München, Germany.
J Bone Joint Surg Am. 2013 Apr 3;95(7):644-51. doi: 10.2106/JBJS.L.00205.
Differentiation between septic and aseptic loosening of joint replacements is essential for successful revision surgery, but reliable markers for the diagnosis of low-grade infection are lacking. The present study was performed to assess intra-articular and systemic levels of antimicrobial peptides and proinflammatory cytokines as diagnostic markers for periprosthetic joint infection.
Fifteen consecutive patients with staphylococcal periprosthetic joint infections and twenty control patients with aseptic loosening of total hip and knee replacements were included in this prospective, single-center, controlled clinical trial. Expression of the antimicrobial peptides human β-defensin-2 (HBD-2), human β-defensin-3 (HBD-3), and cathelicidin LL-37 (LL-37) was determined by ELISA (enzyme-linked immunosorbent assay) in serum and joint aspirates. Proinflammatory cytokines were assessed in serum and joint aspirates with use of cytometric bead arrays. C-reactive protein in serum, microbiology, and histopathology of periprosthetic tissue served as the "gold standard" for the diagnosis of infection.
The antimicrobial peptides HBD-3 and LL-37 were significantly elevated in joint aspirates from patients with periprosthetic joint infection compared with patients with aseptic loosening, and the area under the curve (AUC) in a receiver operating characteristic curve analysis was equal to 0.745 and 0.875, respectively. Additionally, significant local increases in the proinflammatory cytokines interleukin (IL)-1β, IL-4, IL-6, IL-17A, interferon (IFN)-γ, and tumor necrosis factor (TNF)-α were observed to be associated with infection. Logistic regression analysis indicated that the combination of an antimicrobial peptide with another synovial fluid biomarker improved diagnostic accuracy; the AUC value was 0.916 for LL-37 and IL-4, 0.895 for LL-37 and IL-6, 0.972 for HBD-3 and IL-4, and 0.849 for HBD-3 and IL-6. In contrast, the only antimicrobial peptides and cytokines in serum that showed a significant systemic increase in association with infection were HBD-2, IL-4, and IL-6 (all of which had an AUC value of <0.75).
The present study showed promising results for the use of antimicrobial peptides and other biomarkers in synovial fluid for the diagnosis of periprosthetic joint infection, and analysis of the levels in synovial fluid was more accurate than analysis of serum.
区分关节置换术后的感染性和无菌性松动对于成功进行翻修手术至关重要，但目前缺乏可靠的标志物来诊断低度感染。本研究旨在评估关节内和全身抗菌肽和促炎细胞因子水平作为假体周围关节感染的诊断标志物。
本前瞻性、单中心、对照临床试验纳入了 15 例确诊为葡萄球菌假体周围关节感染的连续患者和 20 例因无菌性髋关节和膝关节置换术后松动的对照患者。通过酶联免疫吸附试验（ELISA）检测血清和关节抽吸液中抗菌肽人β防御素-2（HBD-2）、人β防御素-3（HBD-3）和抗菌肽 LL-37 的表达。采用流式细胞术微珠阵列检测血清和关节抽吸液中的促炎细胞因子。血清 C 反应蛋白、微生物学和假体周围组织的组织病理学检查作为感染诊断的“金标准”。
与无菌性松动患者相比，关节置换术后感染患者的关节抽吸液中抗菌肽 HBD-3 和 LL-37 显著升高，ROC 曲线分析的 AUC 分别为 0.745 和 0.875。此外，还观察到局部炎症细胞因子白细胞介素（IL）-1β、IL-4、IL-6、IL-17A、干扰素（IFN）-γ和肿瘤坏死因子（TNF）-α的显著增加与感染有关。Logistic 回归分析表明，联合使用抗菌肽和另一种滑液生物标志物可提高诊断准确性；LL-37 和 IL-4 的 AUC 值为 0.916，LL-37 和 IL-6 的 AUC 值为 0.895，HBD-3 和 IL-4 的 AUC 值为 0.972，HBD-3 和 IL-6 的 AUC 值为 0.849。相比之下，与感染相关的唯一在血清中系统性升高的抗菌肽和细胞因子是 HBD-2、IL-4 和 IL-6（所有 AUC 值均<0.75）。
本研究表明，抗菌肽和其他生物标志物在关节滑液中用于诊断假体周围关节感染具有良好的应用前景，滑液分析比血清分析更准确。
