A Diagnostic Serum Antibody Test for Patients With Staphylococcus aureus Osteomyelitis
A Diagnostic Serum Antibody Test for Patients With Staphylococcus aureus Osteomyelitis
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DOI：
10.1007/s11999-015-4354-2
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发表时间：
2015-09-01
影响因子：
4.2
通讯作者：
Daiss, John L.
中科院分区：
文献类型：
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作者：
Nishitani, Kohei;Beck, Christopher A.;Daiss, John L.
背景由于对金黄色葡萄球菌的免疫力尚未完全阐明，因此没有诊断测试来衡量患者的宿主反应可能有多强。因此，我们的目的是开发一个测试血清中的特异性抗体与诊断和预后potential.Questions/Purposes我们描述的开发和验证的多重免疫测定，用于表征患者的免疫反应对14个已知的金黄色葡萄球菌抗原，然后我们用来回答四个问题：（1）某些抗原占主导地位的免疫反应对金黄色葡萄球菌？(2)感染的病人和小鼠是否有一种主要的抗原识别模式？(3)免疫球蛋白G（IgG）对任何单一抗原的反应是否是持续性金黄色葡萄球菌感染的有用预测因子？(4)测量对所有14种抗原的联合应答是否能更好地预测持续感染？方法采用病例对照研究。从35例连续的金黄色葡萄球菌培养证实的（甲氧西林敏感金黄色葡萄球菌或耐甲氧西林金黄色葡萄球菌）肌肉骨骼感染（深部植入物相关、骨髓炎和已确定的脓毒性关节炎病例）患者中收集血清。仅当患者未提供参与的知情同意书时才将其排除。24例患者在全关节置换术后发生植入物感染，5例患者发生骨折植入物感染，4例患者发生自体膝关节感染，2例患者发生慢性骨髓炎（无植入物）。对照组患者选自一组健康的、经医学优化的患者，这些患者计划接受择期关节成形术。对照组患者的年龄（+/- 3岁）、BMI（+/- 3 kg/m2）和性别尽可能与感染患者匹配。来自金黄色葡萄球菌感染和鼠金黄色葡萄球菌胫骨植入物感染患者的血清用于评价针对14种重组金黄色葡萄球菌抗原的免疫球蛋白滴度的多重免疫测定。所有患者均接受了针对微生物的抗生素治疗和适当、及时的手术治疗。通过临床检查、红细胞沉降率、C-反应蛋白和根据需要对病原体感染部位进行复筛来监测治疗反应。炎症标志物升高或持续阳性培养结果被认为是持续感染的证据。提供的治疗被认为是标准的护理治疗，在我们的医疗中心和所有的患者共同治疗与董事会认证的传染病specialist.Results四个抗原引起超过65%的可测量的IgG，最占主导地位的是对铁调节的表面决定簇蛋白B（IsdB）。感染患者IgG滴度升高的模式不同，因此在50%以上的感染患者中没有单一滴度升高（曲线下面积[AUC]）
Background Because immunity against Staphylococcus aureus has not been fully elucidated, there is no diagnostic test to gauge how robust a patient's host response is likely to be. Therefore, we aimed to develop a test for specific antibodies in serum with diagnostic and prognostic potential.Questions/Purposes We describe the development and validation of a multiplex immunoassay for characterizing a patient's immune response against 14 known S aureus antigens, which we then used to answer four questions: (1) Do certain antigens predominate in the immune response against S aureus? (2) Is there a predominant pattern of antigens recognized by patients and mice with infections? (3) Is the immunoglobulin G (IgG) response to any single antigen a useful predictor of ongoing S aureus infection? (4) Does measurement of the combined response against all 14 antigens provide a better predictor of ongoing infection?Methods A case-control study was performed. Sera were collected from 35 consecutive patients with S aureus culture-confirmed (methicillin-sensitive S aureus or methicillin-resistant S aureus) musculoskeletal infections (deep implant-associated, osteomyelitis, and cases of established septic arthritis). Patients were excluded only if they did not give informed consent for participation. Twenty-four patients had implant infections after total joint replacements, five had fracture implant infections, four had native knee infections, and two had chronic osteomyelitis without an implant. Control patients were chosen from a group of healthy, medically optimized patients scheduled to undergo elective arthroplasty. Control patients were matched for age (+/- 3 years), BMI (+/- 3 kg/m(2)), and sex as closely as possible to patients with infections. Sera from patients with S aureus infections and murine S aureus tibial implant infections were used to evaluate a multiplex immunoassay for immunoglobulin titers against 14 recombinant S aureus antigens. All patients were treated with organism-targeted antibiotic therapy and appropriate, timely surgery. Treatment response was monitored with clinical examination, erythrocyte sedimentation rate, C-reactive protein, and resampling of the infection site for the pathogen as needed. Elevated inflammatory markers or persistent positive culture results were considered evidence of ongoing infection. Treatment provided was considered standard-of-care therapy in our medical center and all patients were treated jointly with a board-certified infectious disease specialist.Results Four antigens elicited more than 65% of the measurable IgG, the most dominant being against iron-regulated surface determinant protein B (IsdB). Patients with infections had different patterns of elevated IgG titers, so that no single titer was elevated in more than 50% of patients with infections (area under the curve [AUC]