小剂量利妥昔单抗治疗复发难治性原发免疫性血小板减少症的临床观察

目的 探讨小剂量利妥昔单抗治疗复发难治性原发免疫性血小板减少症(ITP)的疗效及安全性.方法 研究纳入20例复发难治性ITP患者,给予利妥昔单抗100 mg静脉滴注,每周1次,连用4周,动态观察血常规、肝肾功能及凝血功能.采用流式细胞术检测治疗前后CD3+、CD4+、CD8+、CD19+淋巴细胞数.免疫比浊法定量检测治疗前后血清免疫球蛋白(IgG、lgM、IgA)水平.用ELISA方法检测血小板膜糖蛋白抗体.治疗前后各项检测指标比较采用配对t检验.结果 治疗后中位起效时间为18d,PLT达峰值时间为(24±7)d.治疗后PLT[(124±106)×109/L]显著高于治疗前[(13±5)×109/L](P＜0.01).11例(55％)患者达完全反应(CR),4例(20％)有效(R),5例(25％)无效(NR).中位疗效持续时间为8(5～23)个月.治疗前后外周血WBC、HGB、血清免疫球蛋白以及CD3+、CD4+、CD8+淋巴细胞数无明显变化,CD19+淋巴细胞数治疗后[(50.53±29.11)×106/L]较治疗前[(125.65±14.12)×106/L]明显下降(P＜0.01).3例患者治疗前血小板自身抗体检测阳性,治疗后均为阴性.1例患者在首次输注利妥昔单抗后发生轻微不良反应.结论 小剂量利妥昔单抗是一种治疗复发难治性ITP安全有效的药物,但其最佳用药方案、长期疗效以及不良反应有待临床进一步观察验证.     

小剂量利妥昔单抗在特发性血小板减少性紫癜病人治疗中的观察及护理

目的探讨小剂量利妥昔单抗治疗特发性血小板减少性紫癜(ITP)的护理方法。方法采用小剂量利妥昔单抗治疗ITP患者31例,用药前30min给予预处理,及时准确用药,监测生命体征,观察并及时处理不良反应。结果 31例患者中完全缓解(CR)6例,有效(R)13例,无效(NR)12例,不良反应4例。结论小剂量利妥昔单抗是一种新的治疗方法,应用过程中密切观察、有效护理,对于减轻不良反应、提高疗效非常重要。     

利妥昔单抗治疗难治性免疫性血小板减少性紫癜31例分析

目的 探讨利妥昔单抗(抗CD20单抗)治疗难治性免疫性血小板减少性紫癜(ITP)的安全性和有效性.方法 应用利妥昔单抗(375mg/m2,静脉输注,每周1次,连用4周)治疗31例难治性ITP患者.结果 10例获完全缓解(32.3％),13例获部分缓解(41.9％),5例微效(16.1％),3例无效(9.7％).均无明显不良反应.结论 利妥昔单抗可能是治疗难治性ITP安全、有效的药物.     

两种小剂量利妥昔单抗治疗方案治疗原发免疫性血小板减少症疗效比较

目的 比较两种小剂量利妥昔单抗治疗方案治疗成人原发免疫性血小板减少症(ITP)的疗效。方法 51例ITP患者非随机分为两组:A组31例患者利妥昔单抗用量为100 m g/周,连续4周;B组20例患者利妥昔单抗用量为375 mg/m2,只用1次。结果 A组:总有效(OR)率和完全反应(CR)率分别为58％和29％,中位反...     

小剂量利妥昔单抗治疗继发于结缔组织病的血小板减少症七例临床研究

目前,继发于结缔组织病(CTD)的血小板减少症被归人继发性免疫性血小板减少症(sITP)的范畴[1].相对于原发免疫性血小板减少症(ITP),继发于结缔组织病的免疫性血小板减少症(CTD-sITP)发病机制更为复杂[2],但两者的发病机制也存在一些共性,例如都存在血小板糖蛋白抗体以及T、B淋巴细胞的免疫耐受损伤[2-3].利妥昔单抗作为一种抗CD20的嵌合型单克隆抗体,具有B淋巴细胞清除作用.标准剂镀和小剂量利妥昔单抗治疗ITP疗效较好[4-7].     

小剂量利妥昔单抗治疗慢性特发性血小板减少性紫癜疗效分析

目的 探讨小剂量利妥昔单抗(抗CD20单抗)治疗慢性特发性血小板减少性紫癜(ITP)临床疗效、安全性及患者免疫学改变.方法 采用小剂量利妥昔单抗(100 mg,每周1次,共4次)治疗26例对糖皮质激素和免疫球蛋白治疗无效的慢性ITP患者,检测治疗前后血常规,免疫球蛋白和血小板相关抗体及淋巴细胞亚群CD3~+、CD3~+CD4~+、CD3~+CD8~+、CD3~- CD56~+、CD4~+ CD25~+、CD4~+ CD25~+ FOXP3~-、CD4~+ CD25~+ FOXP3~+和CD19~+CD20~+细胞.结果 26例患者,完全缓解(CR)6例(23.1%),有效(R)10例(38.5%),其中l例复发,无效(NR)10例(38.5%).中位随访时间5.5(0.8-8)个月,起效和达CR中位时间分别为27(1-104)d和41(4-109)d.治疗前后免疫球蛋白定量和CD3~+、CD3~+CD4~+、CD3~+CD8~+、CD3~- CD56~+、CD4~+CD25~+、CD4~+ CD25~+ FOXP3~+细胞计数差异无统计学意义.治疗后的CD4~+CD25~+FOXP3~-细胞计数比治疗前降低(P<0.05).治疗后的CD19~+CD20~+细胞计数与治疗前相比明显减少(P<0.01).治疗后血小板相关抗体PAIgG比治疗前减低(P<0.05).26例患者均无明显的不良反应.结论 小剂量利妥昔单抗可能是一种高效、安全治疗ITP的药物,但其最佳用药方案、长期疗效以及不良反应仍有待临床进一步观察.     

难治性免疫性血小板减少性紫癜不同治疗方法的疗效比较

目的:比较免疫性血小板减少性紫癜(ITP)不同治疗方法的疗效,探讨利妥昔单抗治疗难治性ITP的安全性和有效性.方法:125例ITP患者,分别应用糖皮质激素、丙球、达那唑、免疫抑制剂等治疗,其中5例难治性ITP患者应用利妥昔单抗375 mg·m-2,静脉输注,每周一次,连用4周.结果:ITP的一线治疗总反应率达70%.利妥昔单抗治疗的5例难治性ITP患者,2例获完全缓解(CR),1例获部分缓解(PR),1例微小反应(MR),1例没有反应.没有急性和迟发的毒性反应.结论:利妥昔单抗可能是治疗难治性ITP安全、有效的药物.     

转化生长因子β1对树突细胞功能的影响

目的研究转化生长因子β1(TGF-β1)对树突细胞(dendritic cells,DC)功能的影响.方法在培养体系中应用不同的细胞因子培养未成熟DC(imDC,GM-CSF)和TGF-β1处理的DC(TGFβ-DC,GM-CSF+TGF-β1),观察其对脂多糖(LPS)刺激的反应.透射电镜观察细胞超微结构,流式细胞仪检测细胞表型,BrdU ELISA法检测DC刺激异基因T细胞增殖的能力,ELISA法检测DC在LPS刺激后分泌IL-12p70的水平,逆转录-聚合酶链反应(RT-PCR)方法检测Toll-like受体4(TLR4)表达.结果与imDC相比,TGFβ-DC在LPS刺激后仍能保持未成熟的细胞形态.TGFβ-DC的CD80,CD86表达明显低于imDC[(4.14±0.95)%和(13.90±7.22)%;(8.60±0.75)%和(20.63±5.03)%,P值均＜0.05].ImDC对LPS有更强的反应性,其中I-Ab、CD80升高的幅度明显高于TGFβ-DC(P值分别＜0.01及＜0.05).TGFβ-DC在96 h的混合淋巴细胞反应中,DC/T细胞为14,11时,TGFβ-DC的异基因刺激能力较imDC弱(P值均＜0.05).LPS刺激TGFβ-DC 24 h后分泌IL-12 p70的能力显著低于imDC(P＜0.01),TGFβ-DC较imDC弱表达TLR4(P＜0.05).结论TGFβ能抑制DC共刺激分子的表达,且能抵抗LPS的促成熟作用,并可能与其TLR4的表达下降有关.     

成人慢性原发性ITP患者利妥昔单抗疗效的影响因素及Plt计数预测价值探讨

目的:探讨成人慢性原发性免疫性血小板减少症(ITP)患者利妥昔单抗疗效的影响因素及血小板(Plt)数预测价值。方法:回顾性分析本院2012年1月-2016年12月收治的52例行利妥昔单抗治疗成人慢性原发性ITP患者的临床资料,其中治疗失败32例设为A组,治疗成功20例设为B组,分析影响利妥昔单抗疗效的独立危险因素,观察首次诊断骨髓CD41~+巨核细胞计数对治疗随访1年患者治疗反应率的影响,计算Plt数用于疗效预测时,效能指标及最佳截断点。结果:B组首次诊断骨髓CD41~+巨核细胞数水平高于A组(P0.05)。多因素Logistic回归模型分析结果显示,首次诊断骨髓CD41~+巨核细胞数150是影响利妥昔单抗疗效的独立危险因素(OR=5.40,95%CI:1.82-15.66,P=0.00)。首次诊断骨髓CD41~+巨核细胞数≥150组患者随访1年反应率显著高于150组(P0.05)。B组利妥昔单抗首次治疗后d 3、14、21、30、60、90、180、270和360 Plt数水平显著低于A组(P0.05)。ROC曲线分析结果显示,Plt数最佳截断点为50×10~9/L;利妥昔单抗首次治疗后d14,AUC为0.68(95%CI:0.57-0.78,P=0.00);成人慢性原发性ITP患者利妥昔单抗疗效预测敏感度和特异度分别为48.73%和87.58%;利妥昔单抗治疗后d 30和60 AUC分别为0.74(95%CI:0.64-0.87)(P=0.00)和0.93(95%CI:0.82-0.98)(P=0.00)。结论:成人慢性原发性ITP患者接受利妥昔单抗治疗后,部分可获得长期缓解,但骨髓巨核细胞数150的患者预后较差;同时根据利妥昔单抗治疗后d 14、30及60 Plt数能够有效预测患者的远期疗效,指导治疗的方案制定。     

弥漫大B细胞淋巴瘤患者Bcl-2、p53和CD55表达与利妥昔单抗疗效的相关性研究

目的探讨弥漫大B细胞淋巴瘤（DLBCL）分子标记物Bcl-2、p53及CD55与利妥昔单抗疗效之间的关系。方法回顾性分析69例采用利妥昔单抗联合化疗治疗DLBCL患者的临床资料,采用免疫组化sP法检测Bcl-2、p53及CD55蛋白的表达,分析其表达与利妥昔单抗疗效之间的关系。结果采用利妥昔单抗联合化疗治疗DLBCI。患者完全缓解（CR）38例（55．1％）,部分缓解（PR）20例（29．0％）,总有效率（CR＋PR）为84．1％。Bcl-2表达阳性者的疗效明显好于阴性者（P=0．043）;p53及CD55蛋白的表达与利妥昔单抗疗效无关（P〉0．05）。结论在利妥昔单抗联合化疗治疗的DLBCL患者中,Bcl-2表达阴性者疗效较差,p53蛋白表达则与疗效元关。     

免疫性血小板减少症患者的细胞免疫功能研究

目的探讨免疫性血小板减少症（ITP）患者免疫功能状态。 方法选取2016年5月至2017年2月在中国中医科学院西苑医院与北京中医药大学东方医院门诊就诊的ITP确诊患者40例,其中慢性22例（慢性组）、新诊断9例（新诊断组）、持续性9例（持续性组）,24名健康者作为对照（对照组）。应用流式细胞仪分析Th1、Th2、Th17、Treg、Breg细胞的表达。ITP组与对照组比较采用Wilcoxon检验,多组之间的比较采用Kruskal-Wallis检验。 结果ITP患者Th1、Th1/Th2高于健康对照组[（16.88±9.02）% vs（8.83±5.30）%、（10.9±9.08）% vs（4.61±3.13）%],差异具有统计学意义（Z=-3.753,P=0.001;Z=-3.596,P=0.001）,Th17、Breg、Th17/Treg低于对照组[（1.02±0.37）% vs（1.41±0.38）%、（1.35±1.37）% vs（2.07±0.86）%、（1.01±0.37）% vs（0.3±0.05）%],差异具有统计学意义（Z=-3.141,P=0.002;Z=-5.963,P=0.001;Z=-1.693,P=0.009）。新诊断组、持续性组和慢性组3组的Th1、Th1/Th2均高于健康对照组[（16.12±7.72）% vs（13.11±3.83）% vs（18.75±10.38）% vs（8.83±5.3）%、（11.63±8.77）% vs（7.77±3.43）% vs（12.03±10.65）% vs（4.61±3.13）%],差异具有统计学意义（Z=14.83,P=0.002;Z=13.363,P=0.004）;3组的Th17、Breg、Th17/Treg均低于健康对照组[（0.91±0.28）% vs（0.98±0.54）% vs（1.07±0.33）% vs（1.41±0.38）%、（1.77±1.58）% vs（1.14±0.52）% vs（1.26±1.54）% vs（2.07±0.86）%、（0.15±0.07）% vs（0.16±0.09）% vs（0.18±0.01）% vs（0.3±0.05）%],差异具有统计学意义（Z=10.04,P=0.018;Z=35.731,P=0.001;Z=3.200,P=0.030）;3组Th2细胞和Treg细胞与健康对照组比较差异均无统计学意义（P>0.05）。3组之间Th1、Th1/Th2、Th17、Breg、Th17/Treg等指标比较差异均无统计学意义（P>0.05）。 结论ITP免疫发病机制包括T和B细胞功能紊乱,T细胞表现为Th1/Th2与Th17/Treg失衡。不同分型ITP患者免疫细胞表现差异性不明显。     

Circulating immune complexes and the immune system in hemorrhagic vasculitis

The paper is concerned with the results of studying the concentration of circulating immune complexes and immune system (the number of lymphocyte populations and subpopulations in the peripheral blood, the level of serum immunoglobulins) in 45 patients aged 10 to 72 years with hemorrhagic vasculitis depending on the disease pattern and course before and after the treatment. The patients suffering from hemorrhagic vasculitis manifested appreciable changes in humoral immunity and negligible derangement of cellular immunity associated with dramatic enhancement of complex formation. The intensity of the alterations was discovered to be dependent on the pattern and course of the disease.     

Enhancing immune responses to limit chronic immune activation during SIV

The persistent immune activation that is typical of HIV-1 and SIV infection results in exhaustion and dysfunction of T and B cells; in T cells, this is marked by increased expression and signaling through the inhibitory receptor programmed death-1 (PD-1). Targeting this exhaustion pathway could result in improved antiviral immune responses, but there have been concerns that it would also lead to increased inflammation and immunopathology. In this issue of the JCI, Dyavar Shetty et al. demonstrate that blocking PD-1 actually reduced proinflammatory responses and improved immunity in the gut of SIV-infected rhesus macaques, suggesting that this might have therapeutic potential to prevent opportunistic infections in HIV-infected patients.     

Sepsis-induced immune dysfunction: can immune therapies reduce mortality?

Sepsis is a systemic inflammatory response induced by an infection, leading to organ dysfunction and mortality. Historically, sepsis-induced organ dysfunction and lethality were attributed to the interplay between inflammatory and antiinflammatory responses. With advances in intensive care management and goal-directed interventions, early sepsis mortality has diminished, only to surge later after “recovery” from acute events, prompting a search for sepsis-induced alterations in immune function. Sepsis is well known to alter innate and adaptive immune responses for sustained periods after clinical “recovery,” with immunosuppression being a prominent example of such alterations. Recent studies have centered on immune-modulatory therapy. These efforts are focused on defining and reversing the persistent immune cell dysfunction that is associated with mortality long after the acute events of sepsis have resolved.     

Bystander immune cytolysis

In addition to alloimmune and autoimmune cell lysis, a third category of immune destruction of blood cells should be recognized. This additional immunologic response occurs when cells or tissues are injured by immunologic reactions in which the cells act as "innocent bystanders." One mechanism by which an immune response to an exogenous antigen leads to the destruction of autologous blood cells is the temporary development of autoantibodies. This is actually an alloimmune reaction which results in a temporary state of "pseudo"-autoimmunity. Although originally described as a type of hemolysis of autologous cells, the concept of bystander immune cytolysis has been extended to include other instances in which immune destruction of cells is caused by antibody that is not developed in response to intrinsic antigens on the cell being lysed. In recent years, compelling data have been presented documenting bystander immune cytolysis in a number of different clinical settings, and efforts have been made to define the mechanisms by which this occurs. Physicians must be aware that some examples of immune lysis of autologous cells are, in reality, examples of temporary bystander immune cytolysis rather than true autoimmune disease. Furthermore, some alloimmune hemolytic reactions can result in lysis of bystander cells.     

Oxaliplatin-induced immune pancytopenia

BACKGROUND: Oxaliplatin, a third-generation platinum compound, has been implicated in isolated cases of immune hemolytic anemia and/or immune thrombocytopenia. The first case of severe immune pancytopenia related to oxaliplatin is described. PATIENT AND METHODS: A 79-year-old woman with colorectal cancer was initially treated with 5-fluorouracil and she later received oxaliplatin and leucovorin every 2 to 4 weeks. During the 15th and 17th cycles of chemotherapy she developed thrombocytopenia, hemolysis, and neutropenia. No problems occurred during the 16th cycle without oxaliplatin. Serologic testing including detection of drug-dependent antibodies and autoantibodies was performed with standard techniques. RESULTS: Serologic findings included a positive immunoglobulin G direct antiglobulin test; nonreactive red blood cell (RBC) eluates; platelet (PLT)-bound antibodies to glycophorin (GP) IIb-IIIa, GPIb-IX, and GPIa-IIa; and oxaliplatin-dependent antibodies to PLTs, RBCs, and neutrophils. CONCLUSION: Oxaliplatin may lead to the production of ddabs to RBCs, PLTs, and neutrophils. Thus the risk of immune cytopenias should always be considered in patients treated with oxaliplatin.