再生障碍性贫血患儿血清TNF-α、IFN-γ和T细胞亚群检测的临床意义

目的：探讨再生障碍性贫血患儿血清TNF-α、IFN-γ和T细胞亚群的变化及意义。方法：应用放免法、酶联免疫双抗体夹心法和单克隆抗体检测法对33例再生障碍性贫血患儿进行血清TNF-α、IFN-γ和T细胞亚群检测,并以35名正常健康儿童作对照。结果：再生障碍性贫血患儿血清TNF-α、IFN-γ水平均非常显著地高于正常儿组（P〈0.01）,而CD3、CD4、CD4/CD8比值又非常显著地低于正常儿组（P〈0.01）。结论：再生障碍性贫血患儿血清TNF-α、IFN-γ和T细胞亚群的变化可作为病情和预后判断的重要检测指标。     

再生障碍性贫血细胞免疫功能及可溶性肿瘤坏死因子受体的研究

目前认为细胞免疫异常在再生障碍性贫血(再障，AA)的发病中起重要作用。本研究应用流式细胞术(FCM)分析测定了32例初治AA患者外周血T淋巴细胞亚群分布．以及用酶联免疫吸附分析法(ELISA)检测了骨髓和血清可溶性肿瘤坏死因子受体1和2(sTNF-R1和sTNF-R2)的水平．以探讨细胞免疫及可溶性免疫分子的异常在AA的免疫发病机制中的作用和意义。     

再生障碍性贫血骨髓T淋巴细胞高表达肿瘤坏死因子

由免疫介导的造血功能抑制在再生障碍性贫血 (AA)的发病过程中起重要作用 ,本研究应用流式细胞仪跟踪分析T细胞活化与TNF α释放的相关性 ,并观察其在AA中不同T细胞亚群的变化 ,探讨T细胞极化与AA临床转归的相关性。材料和方法研究对象 :19例经检查符合AA诊断标准的患者进入本研究 ,急性AA 7例 ,其中Ⅰ型 5例 ,Ⅱ型 2例 ;慢性AA 12例 ;女性 8例 ,男性 11例 ,中位数年龄2 3岁 (9～ 5 1岁 ) ,病程 8天～ 11个月。正常对照为年龄相仿的非血液系统疾病正常骨髓标本共 10例。主要试剂 :RPMI 16 40为美国Gibco产品 ,培养板为美国Corning…     

再生障碍性贫血免疫致病机制的研究进展

造血干细胞缺乏导致造血功能衰竭一直被认为是再生障碍性贫血 (ＡＡ)的主要病理机制。最初应用体外造血细胞集落形成证实ＡＡ患者的骨髓中造血细胞明显减少或缺如 ,ＣＤ34 细胞数和集落形成能力均明显低于正常对照组[1] 。然而 ,应用免疫抑制剂如抗胸腺细胞或淋巴细胞球蛋白 (ＡＴＧ或ＡＬＧ)以及环胞菌素Ａ (ＣｙＡ)治疗ＡＡ ,其疗效为 50 %～80 % [2 ,3] ,由此表明既使重型再生障碍性贫血(ＳＡＡ) ,其体内仍有少量造血干细胞的残留 ,且造血干细胞减少可能是免疫功能异常介导的细胞毒性作用所致[4 ,5] 。近年的研究表明 ,由Ｔ淋巴细胞介导…     

再生障碍性贫血患者免疫调节剂治疗前后TNF和IL-2水平变化及意义

为了探讨再生障碍性贫血(AA)的免疫发病机理及抗T淋巴细胞单克隆抗体(McAb-T)的免疫调节治疗作用,采用放射免疫分析法检测30例AA患者McAb-T治疗前后血清肿瘤坏死因子(TNF)和白细胞介素-2(IL-2)水平及其中10例AA外周血单个核细胞(PBMNC)体外诱生TNF和IL-2水平的变化。结果表明,治疗前AA患者血清TNF水平显著增高(p<0.01),PBMNC诱生的TNF和IL-2水平均明显高于正常对照(p<0.01)。治疗后血清TNF和PBMNC诱生的TNF和IL-2水平降低,与对照组比较无显著差异(p>0.05)。提示AA患者存在造血调控因子分泌异常,McAb-T对TNF和IL-2能发挥特异性的免疫调节作用。     

抗胸腺细胞球蛋白（ATG）对再生障碍性贫血患者淋巴细胞亚群的影响

利用ＡＰＡＡＰ桥联免疫酶标技术，对３６例接受ＡＴＧ治疗的再生障碍性贫血（ＡＡ）患者进行了淋巴细胞亚群检测，结果发现，ＡＡ患者外周血Ｔ淋巴细胞亚群ＣＤ＾＋３ＣＤ＾＋４细胞治疗前后无明显变化，但ＣＤ＾＋４／ＣＤ＾＋８比值，ＣＤ＾＋８细胞数目治疗前后却有显著性差异。ＡＡ患者外周血ＨＬＡ－ＤＲ＾＋细胞较正常明显增高，但ＡＴＧ治疗后却有所下降，本研究的结果表明，ＣＤ＾＋８，ＨＬＡＤＲ＾＋细胞增高及ＣＤ＾＋４     

再生障碍性贫血患者免疫调节剂治疗前后TNF和IL—2水平变化…

为了探讨再生障碍性贫血的免疫发病机理及抗Ｔ淋巴细胞单克隆抗体的免疫调节治疗作用，采用放射免疫分析法检测３０例ＡＡ患者ＭｃＡｂ－Ｔ治疗前后血清肿瘤坏死因子和白细胞介素－２水平及其中１０例ＡＡ外周血单个核细胞体外诱生ＴＮＦ和ＩＬ－２水平的变化。结果表明，治疗前ＡＡ患者血清ＴＮＦ水平显著增高，ＰＢＭＮＣ诱生的ＴＮＦ和ＩＬ－２水平均明显高于正常对照。     

重型再生障碍性贫血患者骨髓T细胞克隆的初步研究

目的建立源于重型再生障碍性贫血(重型再障)患者骨髓的T淋巴细胞克隆,以便研究该病的发病机理.方法用免疫分选法分别从1名初诊重型再障患者及对照的骨髓中富集CD34+和CD3+细胞.将CD3+细胞作反应细胞、照射过CD34+细胞作刺激细胞,进行14d单向自身混合淋巴细胞培养.对活细胞作有限稀释和单个细胞分孔接种,与含IL-2和PHA-P的饲养细胞体系共培养.观察挑选细胞生长孔,计算接种率,用泊松(Poisson)分布初步判断单个细胞分离过程成功与否.而后将阳性孔细胞作转孔培养,定期用饲养抚育刺激、常规用IL-2支持增殖以扩大各克隆的数量.用SABC-P免疫细胞化学染色法,初步鉴定各克隆CD4/CD8抗原表型.结果自身混合淋巴细胞培养后的活细胞数,病例为4×103,对照为65.单细胞分离接种培养后,对照组的细胞生长孔数为0;而病例组的培养板上,共有11孔发生细胞增殖,相应的实际接种率是2.1%,未超出Poisson理论接种率值范围(＜26%),判明平均每个增生孔的细胞克隆前体数不大于1.这11个克隆中,9个呈CD4单阳性表型,阳性为98%;2个为CD8单阳性表型,阳性率为98%.结论从1例重型再障患者骨髓中分离出了11株T淋巴细胞克隆.进一步鉴定分析这些克隆的表型和特异性,以及探讨其Th1(Tc1)/(Th2)(Tc2)效应类型等功能表现,对研究重型再障的免疫学机理具有积极的意义.     

再生障碍性贫血患者细胞因子水平观察

为进一步探讨细胞免疫对ＡＡ发病的影响，阐明细胞因子在ＡＡ患者中变化的基础与临床意义，采用酶联免疫试剂盒ＥＬＩＳＡ法对３８例ＡＡ患者及２０例正常人外周血单个核细胞（ＰＢＭＮＣ）培养上清诱生Ｇ－ＣＳＦ，ＩＬ－６，ＴＮＦα，ＩＦＮα及ＩＬ－８水平进行测定，同时采用改良ＡＰＡＡＰ法观察外周血Ｔ细胞亚群及ＨＬＡ－ＤＲ抗原表达，结果ＡＡ患者ＰＢＭＮＣ培养上清中Ｇ－ＣＳＦ阳性率减低，ＩＬ－６，ＴＮＦαＩＦＮα及     

抗T细胞单抗治疗前后再生障碍性贫血患者细胞免疫功能的变化

抗Ｔ细胞单抗治疗前后再生障碍性贫血患者细胞免疫功能的变化马晓星王鲁群①杨道理徐军迟翠芳①（济南军区总医院免疫科，济南２５００３１）中国图书分类号Ｒ５５６．５近年研究表明，Ｔ淋巴细胞及其相关细胞因子在造血调控中发挥重要作用。本研究分析了抗Ｔ细胞单抗（Ｍ...     

再生障碍性贫血患者免疫调节剂治疗前后TNF和IL—2水平变化及意义

为了探讨再生障碍性贫血（ＡＡ）的免疫发病机理及抗Ｔ淋巴细胞单克隆抗体（ＭｃＡｂ－Ｔ）的免疫调节治疗作用，采用放射免疫法检测３０例ＡＡ患者ＭｃＡｂ－Ｔ治疗前后血清肿瘤坏死因子（ＴＮＦ）和白细胞介素－２（ＩＬ－２）水平及其中１０例ＡＡ外周血核细胞（ＰＢＭＮＣ）体外诱生ＴＮＦ和ＩＬ－２水平的变化。结果表明，治疗前ＡＡ患者血清ＴＮＦ水平显著曾高（Ｐ〈０．０１），ＰＢＭＮＣ诱生的ＴＮＦ和ＩＬ－２水平均明显高     

Ultrastructural Characteristics of Nucleated Cells in Bone Marrow of Patients with Acquired Aplastic Anemia

The objective of this study was to investigate the ultrastructural characteristics of nucleated cells in the bone marrow of patients with aplastic anemia (AA). This was done by observing the morphology of nucleated cells in bone marrow aspirates from 20 patients with AA by transmission electron microscopy. Erythroblasts were decreased in all cases and not observed in 6 cases. Nuclear abnormalities, such as pyknosis, karyolysis, karyorrhexis, apoptosis, and “Swiss cheese”-like changes, were found in 10 cases. Focal cytoplasmic necrotic changes and cytolysis were found in 3 cases. There were more megaloblasts in 4 cases. Abnormalities of granulocytes were found in 12 out of 18 cases. Megakaryocytes showed focal cytoplasmic necrotic changes. Most monocytes had dendritic features, including excessive cytoplasm, processes, and large round nuclei in all cases. Other monocytes illustrated typical monocytic features with twisted nuclei, plentiful RER, vacuoles, lysosomes, and prominent Golgi apparatus. Macrophages and hemophagocytes occurred in all cases. The incidence of lymphocytes was high in 17 out of 20 cases and occasionally lymphocytes were enlarged in 8 cases. More plasmacytes and plasmacytoid lymphocytes were found in 5 and 3 cases, respectively. The observations suggest that (1) the universal nuclear injury of erythroblasts may be related to the pathogenetic pathway of AA development; (2) the dendritic cells and hemophagocytes from the mononuclear phagocyte system may play a more critical role in hematopoietic failure of AA, directly and/or indirectly; and (3) besides T lymphocytes, increasing numbers of plasmacytes or plasmacytoid lymphocytes are associated with AA in some cases.     

重型再生障碍性贫血伴肛周脓肿患者的护理体会

目的：探讨对重型再生障碍性贫血伴肛周脓肿患者的护理体会。方法对1例重型再生障碍性贫血伴肛周脓肿的患者实施止血、抗感染以及纠正贫血和肛周特殊护理。结果经过治疗和护理,患者生命体征平稳,肛周疼痛好转,肛周脓肿处破皮,引流通畅、周围皮肤未见发红。结论对重型再障伴肛周脓肿患者,采取有效的对症支持治疗,能充分减低患者的痛苦,降低患者的经济费用,也提高了患者的满意度。     

再生障碍性贫血患者外周血T细胞亚群和T细胞受体表达水平及其意义

采用流式细胞仪及间接免疫荧光法检测30例再生障碍性贫血患者外周血中T细胞亚群及T细胞表面受体表达水平,并与健康对照组相比,结果表明:70％再障患者存在CD4/CD8比例倒置及CD8~+％异常增高;50％再障患者外周血γδ-T细胞亚群及其在T淋巴细胞总体中所占比例均显著增高;而αβT细胞亚群及TirA~+细胞百分率与正常对照组相比无显著性差异。提示:半数以上再障患者外周血中存在异常增多的γδT细胞及Ts细胞亚群。并可通过其直接或间接作用抑制造血,从而导致再障的发生。     

Allogeneic Hematopoietic Stem Cell Transplantation for the Treatment of Severe Aplastic Anemia Patients with Infection: A Single-Center Retrospective Study

To assess the efficacy of allogeneic hematopoietic stem cell transplantation (allo-HSCT) for severe aplastic anemia (SAA) patients with infection, we conducted a retrospective study on 65 SAA patients with infection who received allo-HSCT from August 2012 to December 2016. All patients received antibacterial and/or antifungal therapy before transplantation. The infection status after initial anti-infection therapy was classified as complete response (CR) (n?=?14) or partial response/stable disease (PR/SD) (n?=?51) before transplantation. The median times for myeloid engraftment in the PR/SD and CR groups were 10.5 days (range, 7 to 22) and 10 days (range, 8 to 11), with cumulative incidences of 98% and 100%, respectively. With a median follow-up of 788 days (range, 181 to 1758), patients with PR/SD had comparable results for 3-year estimated overall survival (85.4% versus 92.9%, P?=?.530) and 3-year failure-free survival (82.7% versus 92.9%, P?=?.458) with 14 patients with CR who received contemporaneous transplantation. In multivariate analysis, poor survival outcomes for the entire cohort was significantly associated with poor pretransplantation performance status. This retrospective study indicated that allo-HSCT may be a feasible therapeutic option for SAA patients with infection.     

Effect of Antithymocyte Globulin Source on Outcomes of HLA-Matched Sibling Allogeneic Hematopoietic Stem Cell Transplantation for Patients with Severe Aplastic Anemia

We wanted to evaluate efficacy of porcine antithymocyte globulin (ATG) in HLA-matched sibling donor allogeneic hematopoietic stem cell transplantation (MSD-HSCT) for patients with severe aplastic anemia (SAA). The clinical data of 113 SAA patients who received MSD-HSCT from January 2005 to November 2016 were analyzed retrospectively. Of these, 58 patients received rabbit ATG as a part of conditioning regimen (R-ATG group), whereas the other 55 patients received porcine ATG (P-ATG group). Patient baseline characteristics and donor conditions of the 2 groups were similar, except patients were older and more received peripheral blood stem cell transplantation in the P-ATG group. All patients engrafted in 2 groups. There were significant differences in the incidence of acute (20.7%?±?5.3% versus 43.4%?±?7.0%, P?=?.015) and chronic graft-versus- host disease (GVHD; 20.1%?±?5.8% versus 46.0%?±?7.9%, P?=?.003) between the R-ATG and P-ATG groups. However, there were no significant differences in terms of 3-year overall survival (93.1%?±?3.3% versus 84.4%?±?5.7%, P?=?.235), grades III to IV acute GVHD (3.4%?±?2.4% versus 12.3%?±?4.7%, P?=?.098), moderate to severe chronic GVHD (12.6%?±?4.9% versus 11.5%?±?4.9%, P?=?.905), or graft rejection (7.4%?±?3.6% versus 5.5%?±?3.1%, P?=?.852). There was also no significant difference with regard to the incidence of severe bacterial infection (P?=?.075), invasive fungal disease (P?=?.701), or cytomeglovirus viremia (P?=?.770). P-ATG showed satisfactory efficacy and safety compared with R-ATG in the setting of MSD-HSCT for SAA patients. P-ATG could be a potential alternative preparation for R-ATG, further offering the advantage of lower costs.     

再生障碍性贫血线粒体突变与端粒长度相关性的研究

目的：研究再生障碍性贫血患者线粒体突变及端粒长度情况,了解两者间的相关性。方法选择2010~2014年确诊为再生障碍性贫血的患者45例,留取骨髓及口腔黏膜上皮标本以进行线粒体DNA ( mitochondrial DNA, mtDNA)突变和端粒长度的检测。线粒体全测序检测到了151个突变,分布在18个基因中,其中包括了40个沉默突变及28个框移突变。同时使用HBG作为内参基因,检测了再障患者和健康志愿者端粒的相对长度( relative T/S value,端粒长度)。结果分析发现非沉默突变的mtDNA突变与白细胞数、血红蛋白水平及血小板数成负相关。端粒长度与白细胞数、血红蛋白水平及血小板数成正相关性,而且非沉默突变的mtDNA突变与端粒长度呈负相关性。结论研究提示突变导致线粒体氧化呼吸链功能紊乱及端粒的缩短是再障患者骨髓衰竭病程中的一个重要因素,而且这两者还会互相影响。     

Comparable Outcomes after HLA-Matched Sibling and Alternative Donor Hematopoietic Cell Transplantation for Children with Fanconi Anemia and Severe Aplastic Anemia

Fanconi anemia (FA)-associated severe aplastic anemia (SAA) requires allogeneic hematopoietic cell transplantation (HCT) for cure. With the evolution of conditioning regimens over time, outcomes of alternative donor HCT (AD-HCT) have improved dramatically. We compared outcomes of HLA-matched sibling donor HCT (MSD-HCT; n?=?17) and AD-HCT (n?=?57) performed for FA-associated SAA at a single institution between 2001 and 2016. Overall survival at 5 years was 94% for MSD-HCT versus 86% for AD-HCT, neutrophil engraftment was 100% versus 95%, platelet recovery was 100% versus 89%, grade II-IV acute graft-versus-host disease (GVHD) was 6% versus 12%, grade III-IV acute GVHD was 6% versus 4%, and chronic GVHD was 0 versus 7%, with no statistically significant differences by type of transplant. The use of UCB was associated with decreased rates of neutrophil recovery in AD-HCT and platelet recovery in both MSD-HCT and AD-HCT. A trend toward a higher serious infection density before day +100 post-HCT was observed in AD-HCT compared with MSD-HCT (P?=?.02). These data demonstrate that AD-HCT should be considered at the same time as MSD-HCT for patients with FA-associated SAA.