中性粒细胞CD64表达在疾病诊疗中的应用进展

中性粒细胞CD64的表达可用于细菌感染所引起的感染性疾病的早期诊断,如败血症,呼吸道感染,烧伤和术后感染等,以及自身免疫性、炎症性疾病的活动期和合并感染的鉴别诊断.不同的临界值的划分,使中性粒细胞CD64表达也可应用于非感染性炎症性疾病的活动性和严重程度判断.若将CD64联合其他炎症性指标共同检测,可提高诊断的敏感性和特异性,也可更好地鉴别细菌感染和病毒感染.中性粒细胞CD64表达的检测有利于疾病辅助诊断、病情监测、预后判断、疗效评估、以及指导临床用药等,具有广阔的临床应用前景.     

流式细胞术检测中性粒细胞CD64指数在鉴别早期感染性疾病中的临床价值分析

目的 分析流式细胞术检测中性粒细胞CD64指数在鉴别早期感染性疾病中的临床价值.方法 选取我院2015年10月至2017年4月期间收治的感染性疾病患者200例,根据感染严重程度分为早期局部感染组(n=120)和脓毒血症组(n=80),另选同期入院体检的健康志愿者50例作为对照组.所有研究对象均于入院后24 ～ 48h内及治疗前进行血常规WBC检测和CRP测定,采用流式细胞仪多参数分析中性粒细胞CD64 (MESF)及中性粒细胞CD64指数,通过绘制受试者工作特征(ROC)曲线计算中性粒细胞CD64指数鉴别早期感染性疾病的灵敏度和特异性.结果 对照组、早期局部感染组、脓毒血症组中性粒细胞CD64及血清CRP、WBC水平依次显著升高,各组差异有统计学意义(P＜0.05).早期局部感染组中性粒细胞CD64指数与血浆CRP、WBC水平呈正相关(P＜0.05).中性粒细胞CD64指数、CRP、WBC的曲线下面积分别为0.896、0.757、0.629(P均＜0.05);与CRP、WBC相比,中性粒细胞CD64指数鉴别早期感染性疾病的灵敏度、特异性为97.39％、90.59％明显升高.结论 分析外周血中性粒细胞CD64指数对于早期感染性疾病的鉴别诊断有重要价值,其诊断效能明显优于血常规WBC和CRP检测.     

中性粒细胞CD64、CD32指数在肝硬化并自发性细菌性腹膜炎诊断中的价值

目的:探讨肝硬化患者腹水中性粒细胞CD32指数(n CD32 ID)、中性粒细胞CD64指数(n CD64 ID)和血清C反应蛋白(CRP)在肝硬化并自发性细菌性腹膜炎(SBP)中的诊断价值。方法:采用回顾性分析方法对入选的156例肝硬化患者进行腹水CD32、CD64流式检测及血清CRP检测,检测结果进行受试者特征曲线(ROC)分析。结果:SBP组n CD32 ID、n CD64 ID和CRP均明显高于非SBP组(P0.001),ROC曲线分析结果显示n CD32 ID、n CD64 ID和CRP的敏感性和特异性分别为:82.8%、96.2%、72.5%和81.0%、95.8%、73.1%。结论:n CD64 ID与n CD32 ID和CRP相比在诊断肝硬化并发自发性细菌性腹膜炎中具有更高的敏感性和特异性,是一种较好的肝硬化并自发性细菌性腹膜炎的早期鉴别诊断指标。     

降钙素原、中性粒细胞CD64、IL-6和CRP检测在新生儿感染性疾病中的诊疗价值

为探讨降钙素原(procalcitonin,PCT)、中性粒细胞CD64、IL-6和CRP早期诊断新生儿感染性疾病及判断预后的价值,选择感染患儿,根据临床表现及血常规、细菌学培养等检查结果确定为细菌组60例、病毒组50例,分别在入院治疗前及治疗3 d后采集空腹血进行PCT、中性粒细胞CD64、IL-6及CRP水平测定,对照组(60例,同期住院的非感染患儿)检测其PCT、中性粒细胞CD64、IL-6及CRP水平,进行统计学分析。采用双抗体夹心免疫层析法测定血清PCT和IL-6水平;采用FCM测定中性粒细胞CD64百分比;采用Aristo特定蛋白分析仪测定CRP水平。结果显示,治疗前细菌组PCT、中性粒细胞CD64、IL-6和CRP水平均明显高于病毒组和对照组(P0.05);病毒组与对照组比较,PCT、中性粒细胞CD64、IL-6和CRP水平差异无统计学意义(P 0.05)。PCT、中性粒细胞CD64、IL-6和CRP诊断新生儿细菌感染性疾病的截断值分别为:0.56 ng/mL、7.01%、8.79 pg/mL、14.5 mg/L。治疗后有效组PCT、中性粒细胞CD64、IL-6和CRP水平与治疗前比较均明显下降(P0.05),治疗后无效组PCT、中性粒细胞CD64和IL-6水平与治疗前比较均无明显变化(P 0.05)。提示PCT作为早期检测感染性疾病的标志物,对新生儿细菌感染更为敏感,而PCT、中性粒细胞CD64、IL-6和CRP可作为新生儿感染性疾病早期诊断、疗效判断的重要指标。     

CD64表达对烧伤感染诊断的价值

目的观察烧伤感染时中性粒细胞表面CD64（Fcγ-RI）表达水平，探讨CD64对烧伤感染诊断的意义。方法选择重度以上烧伤患者78例分为脓毒症组、感染组、非感染组，通过流式细胞仪检测中性粒细胞表面CD64分子的变化并与C反应蛋白（CRP），白细胞（WBC）进行统计学比较。结果脓毒症组的CD64的表达是（83．81±14．98）％，显著高于感染组（40．15±13．45）％和对照组（13．73±5．93）％（P均〈0．01）。感染组与对照组CD64表达水平比较差异也有统计学意义（P〈0．01）。结论烧伤感染时血中性粒细胞表面CD64表达水平明显增加，可考虑作为烧伤感染诊断指标。     

hs-CRP对细菌、真菌感染早期鉴别的意义

目的:探讨超敏C-反应蛋白(hs-CRP)在细菌、真菌感染早期鉴别中的价值.方法:采用免疫荧光法测定革兰阴、阳性细菌感染各50例、真菌感染患者50例及50例病毒感染者(对照组)的血清hs-CRP水平,同时观察白细胞(WBC)、中性粒细胞(PMN)、中性粒细胞比值(N)等炎性指标变化,分析其与不同细菌感染、真菌感染之间的...     

中性粒细胞CD64、PCT联合CRP诊断儿童脓毒血症的价值

目的 探讨中性粒细胞CD64、降钙素原（PCT）和C-反应蛋白（CRP）联合检测在儿童脓毒血症早期诊断中的价值。方法选取2017年1月~2018年12月鄂尔多斯市中心医院儿科收治的55例脓毒血症患儿作为观察组,将同期的55例非感染性疾病患儿作为对照组。分别采用流式细胞术、电化学发光法、免疫透射比浊法检测两组患儿入院时中性粒细胞CD64水平、血清PCT浓度、CRP浓度,比较三种指标独立检测和联合检测诊断儿童脓毒血症的灵敏度、特异度、阳性预测值及阴性预测值;分析观察组治疗前后中性粒细胞CD64、CRP、PCT水平变化情况。结果 入院时观察组中性粒细胞CD64、PCT及CRP水平均高于对照组,差异有统计学意义（P＜0.05）;三种指标联合检测诊断儿童脓毒血症的灵敏度、阳性预测值、阴性预测值及准确度最高,分别为85.02%、75.60%、93.21%、90.15%;治疗后观察组患儿中性粒细胞CD64、PCT 和CRP水平均低于治疗前,差异有统计学意义（P＜0.05）。结论 中性粒细胞CD64、PCT及CRP联合检测能有效提高儿童脓毒血症早期诊断率,为临床治疗提供参考依据。     

CD64的表达在成人麻疹并发细菌性肺炎患者中的诊断价值

目的 探讨中性粒细胞CD64的表达在麻疹并发细菌性肺炎患者的临床价值.方法 选取成人麻疹肺炎患者106例,按临床表现和细菌学检测结果 分为麻疹合并细菌性肺炎组及麻疹合并病毒肺炎组,应用流式细胞术测定中性粒细胞CD64,同时测外周血C反应蛋白（CRP）和白细胞.结果 麻疹合并细菌性肺炎组出疹期CD64水平为（32.15±11.07）MFI,明显高于恢复期（10.6±3.23）MFI（P＜0.01）和麻疹合并病毒性肺炎组（9.55±3.48）MFI（P＜0.01）,以CD64≥8.50MFI、CRP≥10.00 mg/L、WBC≥9.05×109/L阳性标准,三种指标的敏感度分别为78.12%、80.48%、59.37%,特异度分别为76.19、67.67%、64.28%,准确度为77.35%、74.52%、61.32%;CD64与CRP呈正相关.结论 与CRP比较,中性粒细胞CD64的表达可作为麻疹合并细菌性肺炎患者的早期诊断、并可用于判断病情程度的可靠指标之一.     

中性粒细胞CD64指数在儿童感染性疾病诊断中的价值

近年来,临床实验室诊断儿童呼吸道细菌或病毒感染性疾病的常用方法有细菌培养、外周血自细胞计数、中性粒细胞百分比和C反应蛋白（CRP）等,细菌培养是判断感染的金标准,但所需时间长,而且受到一些外在因素的影响。中性粒细胞CD64指数在新生儿感染发生和发展过程中的表达及新生儿败血症中的诊断价值已有不少报道。本文对儿童呼吸道感染性疾病患者进行CD64指数测定,探讨其作为不同病原体感染时的诊断和鉴别诊断的应用价值,现报告如下。     

前降钙素是诊断新生儿严重感染的新指标

严重感染和败血症在NICU占有较高比例,是新生儿死亡常见原因,严重威胁着新生儿的健康,因缺乏典型的临床表现,疾病的早期诊断早期有效治疗极为困难,目前临床上应用的感染性实验室指标如C-反应蛋白(CRP)、白细胞介素-6(IL-6)虽然有助于感染性疾病的诊断,但缺乏特异性.因此需要其它能在感染引起全身炎症反应早期具有提示性的标志物,以能早期诊断给予更特异性的治疗.前降钙素(PCT)可作为感染性疾病的早期诊断指标,具有较高的特异性和敏感性.自Assicot等[1]报道在严重细菌感染者血中升高后已广泛应用于临床,已取得了较好的效果.     

Neutrophil CD64 expression Distinguishing acute inflammatory autoimmune disease from systemic infections

Common bacterial and opportunistic infections are a major cause of mortality in patients who are immunosuppressed due to treatment with corticosteroids or cytotoxic drugs. Common laboratory tests for infection lack sensitivity and specificity. Therefore a new generation of tests to detect early systemic infections has been suggested. One of these tests measures the up-regulation of a Fc receptor (Fcγ R1, or CD 64) on neutrophils. The Fc receptors on white blood cells are very important for effective phagocytosis of bacteria and are up-regulated during an infection. The clinical utility of quantitative CD64 measurements to differentiate between systemic infection and active autoimmune inflammation was examined in an ongoing study. Patients with systemic infection (n = 26), patients with active autoimmune inflammatory disease (n = 45), patients with vasculitis (n = 4) and controls (n = 20) were studied for neutrophil CD64 expression using monoclonal antibodies and flow cytometry. Results from this study concluded that CD64 is up-regulated in systemic infections and some localized infections. Some cases of infection can demonstrate low to intermediate levels of CD64 due to species of bacteria, localized infection and/or length of antibiotic therapy. Ninety-two percent of uninfected patients bind <2000 CD64 antibodies on each neutrophil, while 92% of patients with systemic infections express >2000 CD64 antibodies. These results together with other published studies indicate that quantitative measurement of CD64 is very promising for detection of systemic infection.     

Neutrophil CD64 Expression in Inflammatory Autoimmune Diseases: Its Value in Distinguishing Infection from Disease Flare

The purpose of this research was to clarify the significance of neutrophil CD64 expression in discrimination between infection and disease flare in patients with inflammatory autoimmune diseases. The study included 63 subjects, 20 healthy controls and 43 patients with inflammatory autoimmune diseases (24 with rheumatoid arthritis & 19 with systemic lupus erythematosus). The FC gamma receptor I (CD64 expression) on neutrophils was measured using flow cytometry. The intensity of CD64 expression on neutrophils was significantly elevated in patients with infections; 49.0 (13–205), and active autoimmune disease; 36.15 (12–133) compared to healthy controls; 5.35 (2.6–14) or patients with inactive disease; 7.5 (3.3–18). In the infectious disease group, expression of CD64 was significantly higher than in the active inflammatory disease group, while there was no significant difference between the group of patients with inactive inflammatory disease and healthy controls (P > 0.05). The sensitivity of CD64 bearing neutrophil intensity for detection of infection (using a cut off value of ≥43.5) was 94.4% and specificity was 88.9%. Neutrophil CD64 expression has a good sensitivity and specificity in differentiating infection from disease flare in patients with inflammatory autoimmune diseases. This assay could facilitate early and accurate diagnosis and greatly aid timely institution of appropriate treatment.     

Simultaneous quantitative analysis of FcgammaRI (CD64) expression on neutrophils and monocytes: a new, improved way to detect infections

We performed simultaneous quantitative flow cytometric analysis of neutrophil and monocyte FcgammaRI (CD64) in 289 hospitalized febrile patients. Microbiological evaluation or clinical diagnosis confirmed bacterial (n=89) or viral (n=46) infection in 135 patients. Patient data were compared with data from 60 healthy controls. The average number of FcgammaRI on the surfaces of both neutrophils and monocytes was significantly increased in patients with febrile viral and bacterial infections, compared to healthy controls. Furthermore, we describe a novel marker of febrile infection, designated 'CD64 score point', which incorporates the quantitative analysis of FcgammaRI expressed on both neutrophils and monocytes, with 94% sensitivity and 98% specificity in distinguishing between febrile infections and healthy controls. By contrast, analysis of FcgammaRI expression on neutrophils and monocytes displayed poor sensitivity (73% and 52%) and specificity (65% and 52%) in distinguishing between bacterial and viral infections, and the levels did not differ significantly between systemic (sepsis), local, and clinically diagnosed bacterial infections. In summary, our results clearly show that the increased number of FcgammaRI on neutrophils and monocytes is a useful marker of febrile infection, but cannot be applied for differential diagnosis between bacterial and viral infections or between systemic and local bacterial infections.     

Neutrophil CD64 as a Marker of Bacterial Infection in Acute Exacerbations of Chronic Obstructive Pulmonary Disease

Acute exacerbations of chronic obstructive pulmonary disease (AECOPD) are responsible for most mortality in patients with chronic obstructive pulmonary disease (COPD) and are caused mainly by bacterial infection. We analyzed and compared neutrophil CD64 expression (using the ratio of CD64 level in neutrophils to that in lymphocytes as an index), serum C-reactive protein (CRP), procalcitonin (PCT) levels, white blood cell (WBC) count, and neutrophil percentage among healthy subjects and patients with stable COPD or AECOPD. Compared with patients with COPD and healthy subjects, patients with AECOPD demonstrated significantly increased CD64 index, CRP, PCT, WBC count, and neutrophil percentage. Interestingly, CD64 index and PCT were both significantly higher in patients with AECOPD with positive bacterial sputum culture than those with negative culture. Furthermore, CD64 index and PCT were positively correlated in AECOPD, and there was also correlation between CD64 index and CRP, WBC, and neutrophil percentage. These data suggest that CD64 index is a relevant marker of bacterial infection in AECOPD. We divided patients with AECOPD into CD64-guided group and conventional treatment group. In CD64-guided group, clinicians prescribed antibiotics based on CD64 index; while in the conventional treatment group, clinicians relied on experience and clinical symptoms to determine the necessity for antibiotics. We found that the efficacy of antibiotic treatment in CD64-guided group was significantly improved compared with the conventional treatment group, including reduction of hospital stays and cost and shortened antibiotic treatment duration. Thus, the CD64 index has important diagnostic and therapeutic implications for antibiotic treatment of patients with AECOPD.     

新生儿感染性疾病中性粒细胞CD64分子变化及临床意义

目的观察新生儿感染性疾病中性粒细胞CD64表达水平及其临床意义。方法将34例新生儿感染性疾病患儿根据其临床表现及实验室检查结果分为败血症12例,非败血症感染22例,以同期收治的非感染性新生儿28例为对照组。采用全血流式细胞术、放射酶联免疫吸附试验及特定蛋白分析仪比浊法分别检测三组患儿CD64指数、IL-6、CRP水平。结果败血症组CD64指数、IL-6及CRP水平均高于非败血症感染组和对照组,差异有显著性意义(P<0.05),非败血症感染组CD64指数、IL-6及CRP水平高于对照组(P<0.05);感染组CD64指数与IL-6呈显著的正相关(P<0.01);败血症组CD64指数随病情好转而逐渐降低。结论新生儿周血中性粒细胞CD64表达水平在感染性疾病时显著升高,并随病情而变化,早期检测意义较大。     

Human Neutrophil Lipocalin as a Superior Diagnostic Means To Distinguish between Acute Bacterial and Viral Infections

The distinction between causes of acute infections is a major clinical challenge. Current biomarkers, however, are not sufficiently accurate. Human neutrophil lipocalin (HNL) concentrations in serum or whole blood activated by formyl-methionine-leucine-phenylalanine (fMLP) were shown to distinguish acute infections of bacterial or viral cause with high accuracy. The aim was therefore to compare the clinical performance of HNL with currently used biomarkers. Seven hundred twenty-five subjects (144 healthy controls and 581 patients with signs and symptoms of acute infections) were included in the study. C-reactive protein (CRP), the expression of CD64 on neutrophils, procalcitonin (PCT), and blood neutrophil counts were measured by established techniques, and HNL concentrations were measured in whole-blood samples after activation with fMLP. All tested biomarkers were elevated in bacterial as opposed to viral infections (P < 0.001). CRP, PCT, and CD64 expression in neutrophils was elevated in viral infections compared to healthy controls (P < 0.001). In the distinction between healthy controls and patients with bacterial infections, the areas under the receiver operating characteristic (ROC) curves were >0.85 for all biomarkers, whereas for the distinction between bacterial and viral infections, only HNL concentration in fMLP-activated whole blood showed an area under the ROC curve (AUROC) of >0.90 and superior clinical performance. The clinical performance of HNL in fMLP-activated whole blood was superior to current biomarkers and similar to previous results of HNL in serum. The procedure can be adopted for point-of-care testing with response times of <15 min.     

Shiga toxin-2 induces neutrophilia and neutrophil activation in a murine model of hemolytic uremic syndrome

It has been demonstrated that infections due to Shiga toxins (Stx) producing Escherichia coli are the main cause of the hemolytic uremic syndrome (HUS). Although it is recognized that Stx damage the glomerular endothelium, clinical and experimental evidence suggests that the inflammatory response is able to potentiate Stx toxicity. Lipopolysaccharides (LPS) and neutrophils (PMN) represent two central components of inflammation during a gram-negative infection. In this regard, patients with high peripheral PMN counts at presentation have a poor prognosis. Since the murine model has been used to study LPS-Stx interactions, we analyzed the effects of Stx alone or in combination with LPS on the kinetics of neutrophil production and activation and their participation in renal damage. We observed a sustained neutrophilia after Stx2 injection. Moreover, these neutrophils showed increased expression of CD11b, enhanced cytotoxic capacity, and greater adhesive properties. Regarding the cooperative effects of LPS on Stx2 action, we demonstrated potentiation of neutrophilia and CD11b induction at early times by pretreatment with LPS. Finally, a positive correlation between neutrophil percentage and renal damage (assayed as plasmatic urea) firmly suggests a role for PMN in the pathogenesis of HUS.