Specific Immunoglobulin G Antibody Detected in Umbilical Blood and Amniotic Fluid from a Pregnant Woman Infected by the Coronavirus Associated with Severe Acute Respiratory Syndrome

Specific immunoglobulin G antibody for severe acute respiratory syndrome (SARS) coronavirus was detected in maternal blood, umbilical blood, and amniotic fluid from a pregnant SARS patient. Potential protection of fetus from infection was suggested.     

非典型肺炎病人动态血液分析

目的 :动态检测非典型肺炎 (SARS)病人血液分析结果 ,为SARS病人的诊断、治疗和预防提供帮助。方法 :对本院收治 10 3例SARS病人分别在入院后不同时间段和随访时作血液分析。结果 :SARS病人血液分析结果呈动态变化。入院时 3 1.1%的患者白细胞数减少 ,第 7～ 2 1天升高 ,超过正常值 ,出院时和随访时均正常 ;入院时 3 8.8%患者淋巴细胞数减少 ,第 7～ 2 1天淋巴细胞分类计数低于正常 ;入院时 8.7%患者血小板减少 ,但从住院第 2～ 12天有明显上升 (P <0 .0 5 )。结论 :SARS病人血液分析结果可以协助诊断和疗效判断。     

False positive antibody results against human T-cell lymphotropic virus in patients with severe acute respiratory syndrome

Taiwan suffered from the outbreak of severe acute respiratory syndrome (SARS) in 2003. Our laboratory performed a series of virology and serology tests for SARS patients admitted to our hospital. Cross-reactivity was found when testing for antibody against human T-cell lymphotropic virus (HTLV) in one patient with SARS. Therefore, antibodies against HTLV were examined in paired-sera from 26 SARS patients. ELISA and a neutralization test were used to measure anti-SARS antibodies. Seroconversion for antibody against SARS-CoV was observed in all patients. Surprisingly, with the use of ELISA for HTLV, sera for 13 patients were positive for HTLV (50%), and seroconversion for HTLV was also observed in 10 patients (38.5%). Western blot for HTLV on those 26 paired-sera from 13 HTLV-positive patients displayed 5 positive results for HTLV-I, 7 positive results for HTLV-II, 1 positive result for both HTLV-I and II, 9 negative results for either HTLV-I or HTLV-II, and 4 "indeterminate" results. The findings that antibody to HTLV can be detected in blood samples collected from SARS patients provide important information for safe handling of blood products. Without such knowledge, blood products can be discarded mistakenly even though they contain anti-SARS-CoV antibodies that may be potentially valuable for SARS therapy.     

Serum neopterin for early assessment of severity of severe acute respiratory syndrome

Neopterin and C-reactive protein (CRP) concentrations were determined in serum samples from 129 severe acute respiratory syndrome (SARS) patients and 156 healthy blood donors. In the patients with confirmed SARS, an early neopterin elevation was detected already at the day of onset of symptoms and rose to a maximum level of 45.0 nmol/L 3 days after the onset. All SARS patients had elevated neopterin concentrations (>10 nmol/L) within 9 days after the onset. The mean neopterin concentrations were 34.2 nmol/L in acute sera of SARS patients, 5.1 nmol/L in convalescent sera, and 6.7 nmol/L in healthy controls. In contrast, the mean CRP concentrations in both acute and convalescent sera of SARS patients were in the normal range (<10 mg/L). Serum neopterin level in SARS patients was associated with fever period and thus the clinical progression of the disease, while there was no significant correlation between the CRP level and the fever period. Serum neopterin may allow early assessment of the severity of SARS. The decrease of neopterin level was found after steroid treatment, which indicates that blood samples should be collected before steroid treatment for the neopterin measurement.     

血清新蝶呤水平对SARS病情严重程度的早期评估

目的探讨血清新蝶呤水平与SARS病程及严重程度的关系。方法应用ELISA方法检测129例SARS病人和156例健康献血者的血清新蝶呤含量。结果SARS病人血清新蝶呤水平在症状出现的首日即升高,129份急性期血清中新蝶呤含量平均值为（34.2±20.0）nmol/L,SARS恢复期病人及健康献血者血清中新蝶呤含量在正常范围,急性期血清新蝶呤含量是恢复期的5倍以上。SARS病人血清新蝶呤水平与发热期的长短及疾病的严重程度呈正相关。结论血清新蝶呤水平可作为SARS严重程度的早期指征之一。     

The placentas of patients with severe acute respiratory syndrome: a pathophysiological evaluation

AIMS: The pathology of the placentas delivered from pregnant women who had severe acute respiratory syndrome (SARS) in Hong Kong was studied. METHODS: The pathology of the placentas was retrospectively studied in detail and compared with control sets. The clinical data of the women and neonates were also reviewed. RESULTS: A total of seven placentas were studied. The placentas from two women convalescent from SARS in the first trimester were normal. In three placentas delivered in the acute stage of SARS, there were increases in intervillous or subchorionic fibrin which might be related to disturbances in maternal placental blood flow due to the hypoxic respiratory disease. Extensive fetal thrombotic vasculopathy (FTV) with sharply demarcated zones of avascular fibrotic villi was noted in the placentas of two patients convalescent from SARS in the third trimester. Both pregnancies had intrauterine growth retardation, oligohydramnios and newborns small for gestation. The aetiology of the FTV might be related to thrombotic tendency due to SARS or placental hypoxia. CONCLUSIONS: This report highlights placental pathology that was probably the result of pathophysiological alteration of the maternal fetal unit during SARS. Further studies are required to delineate the relationship between severe maternal respiratory disease, placental pathology and pregnancy outcome.     

SARS肺间质血管病变的病理观察

目的 观察分析严重急性呼吸综合征(severe acute respiratory syndrome，SARS)肺间质血管病变的病理形态学特征。方法 对3例行尸体解剖的SARS病例肺组织进行常规HE染色、组织化学染色和免疫组织化学染色，并探讨其病理形态学特征。结果 死亡的SARS病人肺部病变除弥漫性的肺部损伤(肺泡腔内可见细颗粒样或泡状水肿液、脱落的肺泡上皮细胞；肺泡间隔内表面可见透明膜覆盖，有的区域肺泡腔内出现机化性改变等)外，肺间质内的毛细血管簇状增生及血管壁出现明显的损伤性改变。结论 SARS的肺部血管病变是一个特征性病理形态学变化，可能与SARS病毒的蛋白导致的剧烈免疫反应有关。     

两次随访的康复期SARS患者T细胞亚群及其相关活化分子的研究

目的 :探讨康复期SARS患者外周血T细胞亚群及其相关活化分子的变化。方法 ::对出院后的SARS患者 ,采用统一调查问卷及实验室检测进行随访研究。两次随访中 ,应用流式细胞仪检测了我院 70余例经中西医结合治疗的康复期SARS患者外周血中CD3 、CD4 、CD8 、CD8 CD2 8 、CD8 CD2 8-、CD3 CD2 5 、CD3 CD6 9 、CD3 HLA DR T细胞的百分率及CD4 /CD8 T细胞的比率的改变 ,并以描述性分析及t检验进行比较分析。结果 :两次随访中 ,CD3 、CD4 和CD8 CD2 8 T细胞的百分率 (均值 )及CD4 /CD8 T细胞的比率 ,均明显低于正常值 (P <0 .0 5 ) ,而CD8 CD2 8-T细胞的百分率则显著增高 (P <0 .0 1)。第 2次随访中 ,检测的CD3 、CD8 、CD3 CD2 5 、CD3 CD6 9 及CD3 HLA DR T细胞的百分率 (均值 ) ,及CD4 /CD8 T细胞的比率 ,与第 1次的相比较差异较显著 (P <0 .0 1) ,其余项目差异均不明显。结论 :随着康复期的延长 ,患者的免疫功能逐渐恢复 ,病毒对T细胞活化的影响逐渐减少。     

抗SARS-CoV抗原的人源Fab段噬菌体抗体库的构建

目的 :利用抗SARS冠状病毒IgG抗体阳性的SARS康复患者外周血淋巴细胞 ,构建人源Fab段抗体文库。方法 :制备外周血淋巴细胞总RNA ,逆转录成cDNA。以其为模板 ,利用针对家族特异性Ig基因的引物扩增重链Fd段和轻链基因 ,并重组到噬菌粒载体pComb3中 ,将重组噬菌粒载体电转化大肠杆菌XL 1Blue,酶切鉴定抗体库的重组率 ,并测定噬菌体抗体库的库容量。结果 :构建了源于SARS康复患者血清中抗Fab段的抗体文库 ,轻链、重链Fd段基因的重组率分别为91%和 75 % ,库容量为 7.2 3× 10 7。结论 :成功地构建了抗SARS CoV抗原的人源Fab段噬菌体抗体库     

SARS病人外周血NK细胞和B淋巴细胞的动态变化及发病机理初探

目的：初步探讨外周血NK细胞和B细胞在严重急性呼吸综合征(severe scute respiratory syndrome,SARS)发病进程及发病机理中的意义。方法：应用流式细胞仪检测和分析SARS病人外周血B淋巴细胞、NK细胞动态变化，使用的NK细胞表面标志为CD16^ 、CD56、B细胞表面标志为CD19。结果分析用BD公司的MultiSet自动分析软件。结果：随着病程的进展92％的SABS病人B细胞先降后升或持续升高，少部分病人B细胞无改变或下降。NK细胞显示不同的个体差异，73．7％的病人显示典型的抗病毒免疫现象，即发病初期NK细胞数升高，恢复期NK细胞数下降，也有部分病人NK细胞无变化(15．8％)或升高(10．5％)。结论：在SARS发病进程中B淋巴细胞介导的体液免疫可能起一定的作用。     

Influence of FcgammaRIIA and MBL polymorphisms on severe acute respiratory syndrome

Polymorphisms of human Fc gamma-receptor IIA (FcgammaRIIA) and mannose-binding lectin (MBL) genes have been associated with susceptibility to or severity of some infectious diseases. In order to investigate whether these genetic factors might influence susceptibility to infection with the severe acute respiratory syndrome-associated coronavirus (SARS-Cov) as well as the course and severity of the infection, we evaluated polymorphisms of FcgammaRIIA and MBL genes in DNA samples from a group of approximately 180 people from Hong Kong who were infected with SARS-Cov. These included 132 patients who had moderate course of SARS infection (home subgroup), 26 patients with a severe course requiring treatment in an intensive care ward (ICU subgroup) and a subgroup of 22 patients who died from SARS (deceased subgroup). A total of 200 normal blood donors from the same region were used as controls. A significant association was found between the FcgammaRIIA-R/R131 genotype and a severe course of SARS, with higher frequency of homozygosity for FcgammaRIIA-R/R131 in the ICU subgroup of SARS patients when compared with controls (P=0.03; odds ratio: 3.2; 95% confidence interval: 1.1-9.1). In comparison with controls, a significant difference in linear trend distribution of FcgammaRIIA genotypes was seen among the severe SARS patients (ICU and deceased subgroups) without co-morbidity, and the incidence of FcgammaRIIA-H/H131 was lower in these patients as well. There were no significant differences in MBL genotypes and allele frequencies among SARS patients and controls. The study reveals that in addition to age and co-morbidity, FcgammaRIIA polymorphism of individuals may also influence outcome after infection with the SARS-Cov.     

SARS患者急性期外周血CD3+、CD4+及CD8+细胞数量的变化

目的 探讨SARS患者外周血T淋巴细胞亚群的变化及其临床意义。方法 用全自动血细胞分析仪检测44例SARS患者外周血白细胞计数及分类，用流式细胞仪检测SARS患者外周血T淋巴细胞亚群；并与正常对照组比较。结果 与对照组比较，SARS组患者白细胞总数显著下降，淋巴细胞百分数和绝对数显著下降，粒细胞绝对数显著下降，粒细胞百分数显著增加；CD3^ 、CD4^ 和CD8^ 细胞绝对数显著下降，CD3^ 、CD4^ 及CD8^ 细胞百分数和CD4^ /CD8^ 比值与对照组比较无显著性差异。结论 SARS冠状病毒感染损伤患者细胞免疫功能。     

Longitudinal Analysis of Severe Acute Respiratory Syndrome (SARS) Coronavirus-Specific Antibody in SARS Patients

The serum antibodies to severe acute respiratory syndrome (SARS) coronavirus of 18 SARS patients were checked at 1 month and every 3 months after disease onset. All of them except one, who missed blood sampling at 1 month, tested positive for the immunoglobulin G (IgG) antibody at 1 month. Fifteen out of 17 tested positive for the IgM antibody at 1 month. The serum IgM antibody of most patients became undetectable within 6 months after the onset of SARS. The IgG antibody of all 17 patients, whose serum was checked 1 year after disease onset, remained positive.     

Longitudinal analysis of Severe Acute Respiratory Syndrome (SARS) coronavirus-specific antibody in SARS patients

The serum antibodies to severe acute respiratory syndrome (SARS) coronavirus of 18 SARS patients were checked at 1 month and every 3 months after disease onset. All of them except one, who missed blood sampling at 1 month, tested positive for the immunoglobulin G (IgG) antibody at 1 month. Fifteen out of 17 tested positive for the IgM antibody at 1 month. The serum IgM antibody of most patients became undetectable within 6 months after the onset of SARS. The IgG antibody of all 17 patients, whose serum was checked 1 year after disease onset, remained positive.     

The involvement of natural killer cells in the pathogenesis of severe acute respiratory syndrome

By using peripheral blood samples from 221 cases of severe acute respiratory syndrome (SARS), 34 of Mycoplasma pneumoniae infection, and 44 healthy adults, we measured the total number of natural killer (NK) and CD158b+ NK cells (CD158b+ NK) using flow cytometric analysis and calculated the percentage of CD158b+ NK cells. The total number of NK and CD158b+ NK cells and the percentage of CD158b+ NK cells were significantly lower in patients with SARS than in those with M. pneumoniae infection (P < .05 for all) and healthy subjects (P < .01, P < .01, P < .05, respectively); in 72 patients with severe SARS than in 149 with mild SARS (P < .05 for all); and in 174 cases of SARS with anti-SARS coronavirus-specific IgG and/or IgM antibodies than in 47 without antibodies (P < .05, P < .01, P < .01, respectively). There were no significant differences for the 3 values among patients with SARS without anti-SARS coronavirus antibody, patients with M. pneumoniae infection, and healthy subjects. The number of NK cells and the expression of CD158b on the surface of NK cells changed in patients with SARS and correlated with disease severity and the presence of anti-SARS coronavirus-specific antibodies; SARS differed from M. pneumoniae infection in pathogenesis involving NK cells. Monitoring the total number of NK and CD158b+ NK cells and the percentage of CDD158b+ NK cells might aid in differentiating SARS from M. pneumoniae infection.     

SARS病毒S1蛋白重组C端片段免疫效果的实验研究

为获得纯化的重组SARS病毒S1蛋白C端 ,研究其刺激机体产生针对SARS病毒免疫应答的规律和机制 ,将编码SARS病毒S1蛋白C端 311个氨基酸残基的基因克隆 ,并在原核表达系统中表达 ,纯化获得了的重组蛋白。利用SARS患者恢复期的血清 ,对纯化的重组S1蛋白进行血清学分析。结果表明 ,本研究中克隆表达的重组蛋白序列与公布的SARS病毒S1蛋白C端的序列相同 ,其编码的重组蛋白相对分子质量约为 5 90 0 0Mr。SARS患者恢复期的血清均与重组蛋白反应 ,在5 9 0 0 0Mr处形成特异性的反应条带 ,而来自SARS流行前的正常人对照血清则不能与重组蛋白反应。在本研究中获得的重组蛋白可以为研究SARS病毒识别宿主细胞受体的过程及其机制提供条件。     

严重急性呼吸综合征血细胞动态变化及预测意义

目的探讨严重急性呼吸综合征(SARS)患者血细胞的变化规律,分析SARS预后的临床指征。方法 对43例SAP6患者动态观察血细胞变化规律,做出趋势图,并比较SARS组与正常对照组、SAPS康复组与病死组之间的区别。结果初诊时SARS组白细胞、淋巴细胞、红细胞均低于对照组(P<0.01)差异有显著意义。SARS病死组淋巴细胞和血小板持续降低,康复组则无降低,据此可提示SARS预后。结论动态观察血细胞变化有利于SARS早期诊断及病情预警,从而提示治疗方法,降低病死率。