Division of Clinical Microbiology, Department of Laboratory Medicine and Pathology, Mayo Clinic, Rochester, MN, United States.
Department of Biomedical Statistics and Informatics, Mayo Clinic, Rochester, MN, United States.
Gene. 2022 May 30;825:146400. doi: 10.1016/j.gene.2022.146400. Epub 2022 Mar 17.
Periprosthetic joint infection (PJI), a devastating complication of total joint replacement, is of incompletely understood pathogenesis and may sometimes be challenging to clinically distinguish from other causes of arthroplasty failure. We characterized human gene expression in 93 specimens derived from surfaces of resected arthroplasties, comparing transcriptomes of subjects with infection- versus non-infection-associated arthroplasty failure. Differential gene expression analysis confirmed 28 previously reported potential biomarkers of PJI, including bactericidal/permeability increasing protein (BPI), cathelicidin antimicrobial peptide (CAMP), C-C-motif chemokine ligand 3 (CCL3), 4(CCL4) and C-X-C-motif chemokine ligand 2 (CXCL2), colony stimulating factor 2 receptor beta (CSF2RB), colony stimulating factor 3 (CSF3), alpha-defensin (DEFA4), Fc fragment of IgG receptor 1B (CD64B), intercellular adhesion molecule 1 (ICAM1), interferon gamma (IFNG), interleukin 13 receptor subunit alpha 2 (IL13RA2), interleukin 17D (IL17D), interleukin 1 (IL1A, IL1B, IL1RN), interleukin 2 receptors (IL2RA, IL2RG), interleukin 5 receptor (IL5RA), interleukin 6 (IL6), interleukin 8 (IL8), lipopolysaccharide binding protein (LBP), lipocalin (LCN2), lactate dehydrogenase C (LDHC), lactotransferrin (LTF), matrix metallopeptidase 3 (MMP3), peptidase inhibitor 3 (PI3), and vascular endothelial growth factor A (VEGFA), and identified three novel molecules of potential diagnostic use for detection of PJI, namely C-C-motif chemokine ligand CCL20, coagulation factor VII (F7), and B cell receptor FCRL4. Comparative analysis of infections caused by staphylococci versus bacteria other than staphylococci and Staphylococcus aureus versus Staphylococcus epidermidis showed elevated expression of interleukin 13 (IL13), IL17D, and MMP3 in staphylococcal infections, and of IL1B, IL8, and platelet factor PF4V1 in S. aureus compared to S. epidermidis infections. Pathway analysis of over-represented genes suggested activation of host immune response and cellular maintenance and repair functions in response to invasion of infectious agents. The data presented provides new potential targets for diagnosis of PJI and for differentiation of PJI caused by different infectious agents.
人工关节置换术后感染（PJI）是一种灾难性的并发症，其发病机制尚不完全清楚，有时在临床上难以与其他人工关节置换失败的原因区分开来。我们对 93 个取自关节置换术切除表面的标本中的人类基因表达进行了特征分析，比较了感染性和非感染性人工关节置换失败患者的转录组。差异基因表达分析证实了 28 个先前报道的潜在 PJI 生物标志物，包括杀菌/通透性增加蛋白（BPI）、抗菌肽（CAMP）、C-C 基序趋化因子配体 3（CCL3）、4（CCL4）和 C-X-C 基序趋化因子配体 2（CXCL2）、集落刺激因子 2 受体β（CSF2RB）、集落刺激因子 3（CSF3）、α-防御素（DEFA4）、Fc 片段 IgG 受体 1B（CD64B）、细胞间黏附分子 1（ICAM1）、干扰素γ（IFNG）、白细胞介素 13 受体亚单位α2（IL13RA2）、白细胞介素 17D（IL17D）、白细胞介素 1（IL1A、IL1B、IL1RN）、白细胞介素 2 受体（IL2RA、IL2RG）、白细胞介素 5 受体（IL5RA）、白细胞介素 6（IL6）、白细胞介素 8（IL8）、脂多糖结合蛋白（LBP）、脂钙蛋白（LCN2）、乳酸脱氢酶 C（LDHC）、乳铁蛋白（LTF）、基质金属蛋白酶 3（MMP3）、肽酶抑制剂 3（PI3）和血管内皮生长因子 A（VEGFA），并确定了三个新的潜在用于检测 PJI 的诊断分子，即 C-C 基序趋化因子配体 CCL20、凝血因子 VII（F7）和 B 细胞受体 FCRL4。葡萄球菌和非葡萄球菌与金黄色葡萄球菌和表皮葡萄球菌引起的感染的比较分析显示，葡萄球菌感染中白细胞介素 13（IL13）、IL17D 和 MMP3 的表达增加，金黄色葡萄球菌感染中白细胞介素 1B、IL8 和血小板因子 PF4V1 的表达增加与表皮葡萄球菌感染相比。过度表达基因的途径分析表明，宿主免疫反应和细胞维持和修复功能被激活，以应对感染因子的入侵。所提供的数据为 PJI 的诊断和不同感染因子引起的 PJI 的鉴别提供了新的潜在靶点。
