双歧杆菌对食物过敏小鼠肠道屏障功能及Th1/Th2细胞因子的影响

目的:探讨双歧杆菌在改善食物过敏动物肠道屏障功能、调整肠道菌群结构以及对免疫功能调节方面的作用及其机制.方法:无受试蛋白喂养BALB/c小鼠40只,随机分为4组: 分别于0、3、9 d腹腔注射生理盐水,金黄色葡萄球菌肠毒素B(SEB),卵清蛋白(OVA),SEB+OVA; 并于第7、14天给予OVA灌胃.在SEB+OVA致敏组的基础上设立自然恢复组、双歧杆菌作用组、思密达作用组、双歧杆菌+思密达共同作用组,第15天开始分别经灌胃给予不同的药物,连续7 d,每日1次.培养法分析粪便菌群,检测血清二胺氧化酶(DAO)含量,ELISA法测定血清IgE、IL-4、INF-γ含量.对肠系膜淋巴结(MLN)及肝、肾、肺组织进行培养以探讨有无细菌移位(BT)发生.同时,采用流式细胞术分析其脾细胞悬液中CD4+CD25+调节性T细胞的数量变化.结果:与SEB+OVA实验组相比,双歧杆菌作用组小鼠血清IgE、DAO含量(A 值)、血清IL-4(51.314±3.785 ng/L vs 69.980±9.103ng/L,P<0.05)含量显著降低; 血清INF-γ水平显著升高(194.281±12.144 ng/L vs 133.875±33.822 n g/L,P<0.05); 脾细胞悬液中CD4+CD25+T细胞数量显著升高(5.778%±0.773% vs 4.216%±0.439%,P<0.05); 肠道固有菌群中益生菌乳酸杆菌的含量(6.670±0.443 vs 5.654±0.289,P<0.05)、双歧杆菌的含量(8.611±0.295 vs 7.491±0.339,P<0.05)显著升高,条件致病菌大肠杆菌的含量(5.364±0.537 vs 6.718±0.267,P<0.05)、类杆菌的含量(7.427±0.544 vs 8.606±0.317,P<0.05)显著降低; MLN及外周器官细菌移位率显著降低(12.5% vs 37.5%,P<0.05).结论:双歧杆菌可以有效调节机体免疫功能、调整肠道菌群失调及保护肠道黏膜屏障功能.     

HBV感染后外周血CD4+CD25+Foxp3+调节性T细胞与疾病进展的相关性

目的:探讨HBV感染者外周血CD4~ CD25~ Fox- p3~ 调节性T细胞水平与HBV感染后疾病进程的相关性.方法:HBV感染者136名及健康对照40名,应用流式细胞仪胞内染色技术检测外周血CD4~ CD25~ Foxp3~ 调节性T细胞表达,结合HBV感染者临床情况进行分析.结果:HBV感染者外周血CD4~ CD25~ Foxp3~ 调节性T细胞表达率较健康对照组显著增高(7.48%±1.03% vs 3.58%±0.71%,P<0.01);慢性乙肝组与慢性重型乙肝组相比,外周血CD4~ CD25~ Foxp3~ T调节细胞的表达率有明显差异(6.55%±1.26% vs 8.65%±2.58%,P<0.05);HBV病毒载量的对数值与外周血CD4~ CD25~ Foxp3~ T调节细胞的表达率之间存在正相关(r=0.332,P<0.01).结论:HBV感染者外周血CD4~ CD25~ Foxp3~ 调节性T细胞水平与疾病进展明显相关.     

肺癌患者外周血CD4+ CD25+调节性T细胞的检测及其临床意义

目的检测肺癌患者外周血CD4 CD2 5调节性T细胞的分布并探讨相关机制。方法流式细胞仪分析46例肺癌患者外周血CD4 CD25 调节性T细胞占CD4 T淋巴细胞的比例;并用ELISA方法检测同标本血中转化生长因子-1(TGF-β1)的浓度。结果46例肺癌患者外周血中CD4 CD2 5调节性T细胞占CD4 T淋巴细胞的比例为(19.1±2.3)%,与对照组(4.1±0.6)%比较差异有显著性(P<0.05)。22例鳞癌、19例腺癌、5例小细胞癌患者外周血中CD4 CD2 5调节性T细胞比例分别为(20.1±0.9)%、(18.8±0.4)%、(19.2±0.4)%,各组间比较差异无显著性(P>0.05);均显著高于对照组(4.1±0.6)%,P<0.05;20例Ⅲ、15例Ⅳ晚期肺癌患者外周血中CD4 CD2 5调节性T细胞比例为(21.4±2.1)%、(20.1±1.3%),均显著高于11例Ⅱ期患者(10.6±1.5)%,P均<0.05。肺癌组外周血清中TGF-β1的水平显著高于对照组,且随着TGF-β1浓度的增加,CD4 CD2 5调节性T细胞比例逐渐增高,两者呈正相关(r=0.0615,P<0.05)。结论肺癌患者外周血中有CD4 CD25 调节性T细胞比例增高,且与分期有关。     

TIM1与TIM4对小鼠食物过敏模型中CD4+CD25+调节性T细胞功能的影响

目的:探讨在食物过敏小鼠模型中CD4+CD25+ Treg 细胞的功能状态及TIM4 与TIM1 对其的影响,分析食物过敏的发生机制. 方法:无受试蛋白喂养BALB/c 小鼠32 只,随机分为4组:空白对照组、金黄色葡萄球菌肠毒素B(SEB)+ 卵清蛋白(OVA) 共同作用组、TIM1 抗体干预组及TIM4 抗体干预组,分别于0、3、9 d ip生理盐水,SEB 和OVA,TIM1 抗体+SEB+OVA,TIM4 抗体+SEB+OVA,并于第7、14 天给予SEB+OVA( 空白对照组以生理盐水ig)ig. RT-PCR 检测空肠及脾脏Foxp3 mRNA 表达、空肠TIM4 mRNA 表达,ELISA 法测定血清TGF-β1与IL-10 的表达. 免疫组织化学法检测空肠黏膜TGF-β1与IL-10 表达. 结果:与空白对照组相比,SEB+OVA 共同作用组小鼠空肠及脾脏F oxp3 mRNA 表达明显下降(0.401±0.145 vs 0.732±0.162;0.407 ±0.082 vs 0.691±0.145,均P<0.05),TIM4 mRNA 表达明显增高(P<0.05),血清和空肠黏膜TGF-β1表达显著降低(7859.853±126.704 ng/L vs 8342.814±488.461 ng/L;108.834 ±9.634 ng/L vs 156.298±12.002 ng/L,均P<0.05);与SEB+OVA 组相比,TIM1 和TIM4 抗体干预组小鼠空肠及脾脏F oxp3 mRNA 及血清和空肠黏膜TGF-β1表达显著增高(均P<0.05). 结论:TI M4 与TI M1 抗体干预可恢复SEB+ OVA 致敏小鼠Treg 细胞功能,维持耐受平衡,减轻过敏症状,提示TIM4-TIM1 通路可能在食物过敏的发生中起重要作用.     

CD4+ CD25+调节性T细胞在重型乙型肝炎发病中的作用

目的探讨CD4 CD25 调节性T细胞在重型乙型肝炎病人发病机制中的作用。方法采用流式细胞仪检测30例重型乙型肝炎患者、20例慢性乙型肝炎患者、20例无症状乙肝病毒携带者和10例健康的外周血CD4 CD25 调节性T细胞(CD4 CD25 Treg)的水平,并应用荧光定量PCR方法测定上述研究对象血中HBVDNA滴度。结果(1)重型乙型肝炎组外周血CD4 CD25 调节性T细胞的平均百分率为(2.63±0.83)%,较慢性乙型肝炎组的(4.15±1.17)%有显著差异(P<0.05),较无症状乙肝病毒携带者组及健康对照组则有极其显著差异(P均<0.01);(2)慢性乙型肝炎组外周血CD4 CD25 调节性T细胞的百分率与无症状乙肝病毒携带者及健康对照组,有显著的差异(P<0.05);无症状乙型肝炎携带者组外周血调节CD4 CD25 T细胞的百分率为(8.32±2.72)%,与健康对照组(8.10±2.65)%比较无差异;(3)重型乙型肝炎组外周血HBVDNA滴度为1.2×104拷贝/ml,与慢性乙型肝炎组(2.3×106拷贝/ml)和无症状乙肝病毒携带者(7.8×105拷贝/ml)相比较,有极其显著差异(P均<0.01);慢性乙型肝炎组外周血HBVDNA滴度与无症状乙肝病毒携带者相比,无差异;(4)无症状乙型肝炎携带者;慢性乙型肝炎和重型乙型肝炎,患者外周血CD4 CD25 调节性T细胞的百分率与HBVDNA滴度呈正相关。结论(1)CD4 CD25 调节性T细胞能抑制T细胞对乙型肝炎病毒的免疫反应,从而抑制乙型肝炎病毒诱导的对肝细胞的免疫攻击的发生;(2)不同乙型肝炎病人外周血CD4 CD25 调节性T细胞的百分率与HBVDNA滴度呈正相关,表明CD4 CD25 调节性T细胞数量对体内HBV载量具有较大的影响;(3)CD4 CD25 调节性T细胞在重型乙型肝炎的病情进展及病毒抑制清除等方面起着重要的作用。     

慢性HBV感染患者外周血CD4~+CD25~+调节性T细胞表达及其临床意义

目的探讨CD4+CD25+调节性T细胞与慢性HBV感染后不同临床转归和临床特点的相关性。方法在26例慢性乙型肝炎(CHB)患者、15例无症状HBsAg携带者(ASC)和11例肝炎肝硬化(LC)患者和16例正常对照者,分离外周血单个核细胞(PBMC),采用流式细胞仪检测CD4+CD25+调节性T细胞的表达水平。结果CHB组和ASC组的CD4+CD25+调节性T细胞占CD4+T细胞的百分率分别为4.40±2.76%和4.43±2.10%,均高于正常对照组(2.70±0.97%),差异显著(P0.01);CD4+CD25+调节性T细胞的表达水平与HBVDNA水平无相关性(r=0.018,P0.05);在HBeAg阳性与阴性组患者CD4+CD25+调节性T细胞的表达也无明显的差异(P0.05)。结论慢性HBV感染者外周血CD4+CD25+调节性T细胞水平升高,可能与HBV感染的慢性化有关。     

CD4~+CD25~+调节性T细胞对啮齿类疟原虫感染过程及结局的影响

目的探讨CD4+CD25+调节性T细胞数量在约氏疟原虫(致死型)和夏氏疟原虫混合感染小鼠免疫应答中的动态变化。方法DBA/2和BALB/c小鼠分别经腹腔注射致死型约氏疟原虫(P.y17XL)、夏氏疟原虫(P.cAS)和P.y17XL+P.cAS(1∶1)混合感染的红细胞,计数红细胞感染率;采用流式细胞术动态检测脾细胞中Tregs细胞数量的变化。结果P.y17XL+P.cAS感染的DBA/2小鼠于感染后18d自愈;而BALB/c小鼠于感染过程中虽然出现死亡(8d),但与P.y17XL感染小鼠(5d)相比,死亡时间明显延迟;P.y17XL和P.y17XL+P.cAS感染的DBA/2鼠于感染后第5d CD4+CD25+调节性T细胞数量均达峰值,随后缓慢下降,相比P.cAS感染的DBA/2鼠于感染后第10d达峰值,是其它两种同天感染鼠的3倍和2倍,且小鼠全部死亡;而P.y17XL和P.y17XL+P.cAS感染的BALB/c小鼠CD4+CD25+调节性T细胞数量于感染后均迅速升高,分别于感染后第5d和第8d达30%左右,小鼠全部死亡,相比P.cAS感染的BALB/c小鼠CD4+CD25+调节性T细胞数量于感染后缓慢升高,于感染后第5d达14%,随后开始下降。结论①P.y17XL+P.cAS混合感染DBA/2鼠后CD4+CD25+调节性T细胞数量的动态变化与P.y17XL单独感染表现出完全相同的模式;BALB/c鼠:CD4+CD25+调节性T细胞数量的动态变化与P.y17XL单独感染也表现出完全相同的模式,但变化的时间明显被滞后;②CD4+CD25+调节性T细胞的异常升高与感染结局密切相关。     

系统性红斑狼疮患者外周血CD4+CD25highFoxp3+调节性T细胞数量和Foxp3mRNA的表达水平与疾病活动性的相关性

目的 研究系统性红斑狼疮(SEE)患者CD4+CD25highFoxp3+调节性T细胞的数量及其功能基因Foxp3 mRNA的表达水平与SLE疾病活动性和肾脏损伤的相关性.方法 采用四色流式细胞术以Foxp3-异硫氰酸荧光素(FITC )/CD25-藻红蛋白/CD4-多甲藻叶绿素蛋白(PerCP)/CD3-藻蓝蛋白7抗体组合检测40名健康对照者及42例SLE患者外周血CD4+CD25highFoxp3+调节性T细胞的数量,实时荧光定量聚合酶链反应(PCR)检测特异性转录因子Foxp3 mRNA的表达水平,并分析其与SLE患者疾病活动指数(SLEDAI)、补体C3及血清抗双链DNA(dsDNA)抗体的关系.统计学方法采用t检验和Spearman相关分析.结果 活动期SLE患者外周血CD4+CD25highFoxp3+调节性T细胞数量显著低于健康对照组[(4±3)％与(7±4)％,P＜0.05],稳定期与健康对照组差异无统计学意义(P＞0.05);活动期SLE患者外周血CD4+CD25highFoxp3+调节性T细胞数量及CD4+CD25highFoxp3+调节性T细胞/CD4+比值显著低于稳定期患者[(4±3)％,(9±6)％与(5±4)％,(10±6)％,P均＜0.05];活动期SLE患者外周血Foxp3 mRNA的表达水平明显低于稳定期和对照组(P＜0.01,P＜0.05);SLE患者并发肾病组外周血CD4+CD25highFoxp3+调节性T细胞数量及CD4+CD25highFoxp3+调节性T细胞/CD4+比值显著低于SLE非肾病组(P＜0.05).相关分析显示,SLE患者外周血CD4+CD25highFoxp3+调节性T细胞数量与SLEDAI呈负相关(r=-0.5782,P＜0.05);CD4+CD25highFoxp3+调节性T细胞/CD4+比值与SLEDAI呈负相关(r=-0.4913,P＜0.05),与补体C3呈正相关(r=0.3687,P＜0.05);SLE患者外周血CD4+CD25highFoxp3+调节性T细胞数量与Foxp3 mRNA的表达水平呈正相关(r=0.6142,P＜0.0l).结论 SLE患者外周血CD4+CD25highFoxp3+调节性T细胞和Foxp3 mRNA的变化可能是导致SLE疾病发生和发展的关键因素之一,与疾病的活动性有密切关系.     

吡喹酮治疗前后小鼠脾细胞中CD4+CD25+Foxp3+T细胞变化及其意义

目的 分析吡喹酮治疗前后小鼠脾细胞中CD4+CD25+Foxp3+T细胞的变化.探讨其与血吸虫感染后肝脏免疫病理反应的关系.方法 54只BALB/C小鼠随机分为3组,阳性感染组、吡喹酮治疗组(感染后第6周顿服吡喹酮治疗)及阴性对照组.于感染后第3、6、9周分批处死小鼠,取脾单细胞悬液,经过常规表面染色、打孔、固定、胞内染色后,用流式细胞仪检测分析CD4+CD25+Foxp3+调节性T细胞的变化.结果 感染组第3、6、9周脾细胞中CD4+CD25+Foxp3+T细胞的数量分别为(2.57 4±0.13)%、(1.77±0.21)%、(1.10±0.05)%,其含量逐步下降(P<0.05),治疗组分别为(2.61±0.12)%、(1.82±0.14)%、(1.76±0.11)%,经治疗后其含量变化差异无统计学意义(P>0.05),阴性组差异无统计学意义(P>0.05);CD4+CD25+Foxp3-T细胞和CD4+CD25-Foxp3+T细胞在各组中的含量差异均无统计学意义(P均>0.05)结论CD4+CD25+Foxp3+T细胞在日本血吸虫感染中具有免疫抑制作用,与血吸虫虫卵肉芽肿慢性病变具有相关性,吡喹酮可以通过抑制CD4+CD25+Foxp3+T降低以减缓血吸虫肉芽肿炎性病变的程度.     

慢性丙型肝炎患者CD4+CD25+调节性T细胞表达增加

目的:探讨CD4+CD25+调节性T(Treg)细胞在慢性丙型肝炎患者免疫下调中的意义.方法:流式细胞仪检测慢性丙型肝炎患者外周血中CD4+CD25+Treg细胞的数量;与CD4+CD25-T细胞共同培养,检测其抑制功能;流式细胞仪检测其对CD4+CD25-T细胞合成IFN-γ和IL-4的影响;RT-PCR检测CD4+CD25+Treg细胞中Foxp3的mRNA表达.结果:CD4+CD25+Treg细胞约占慢性丙型肝炎患者外周血中CD4+T细胞的14.1±1.6%,显著高于正常对照5.3±0.8%(P＜0.01),显著抑制CD4+T细胞的增殖(P=0.002),以及合成IFN-γ.CD4+CD25+Treg 细胞高表达Foxp3.结论:持续性HCV感染患者CD4+CD25+Treg细胞表达增加,特异性抑制Th1细胞反应.     

Human CD8+CD25+ thymocytes share phenotypic and functional features with CD4+CD25+ regulatory thymocytes

CD8+CD25+ cells, which expressed high levels of Foxp3, glucocorticoid-induced tumor necrosis factor receptor (GITR), CCR8, tumor necrosis factor receptor 2 (TNFR2), and cytotoxic T-lymphocyte-associated antigen 4 (CTLA-4) mRNAs, were identified in the fibrous septa and medullary areas of human thymus. Activated CD8+CD25+ thymocytes did not produce cytokines, but most of them expressed surface CTLA-4 and transforming growth factor beta1 (TGF-beta1). Like CD4+CD25+, CD8+CD25+ thymocytes suppressed the proliferation of autologous CD25-T cells via a contact-dependent mechanism. The suppressive activity of CD8+CD25+ thymocytes was abrogated by a mixture of anti-CTLA-4 and anti-TGF-beta1 antibodies and it was mediated by their ability to inhibit the expression of the interleukin 2 receptor alpha chain on target T cells. These results demonstrate the existence of a subset of human CD8+CD25+ thymocytes sharing phenotype, functional features, and mechanism of action with CD4+CD25+ T regulatory cells.     

非小细胞肺癌患者CD3+、CD4+、CD8+、CD44+表达的临床研究

目的研究非小细胞肺癌患者外周血淋巴细胞中CD3+、CD4+、CD8+、CD4+4的表达水平。方法取65例非小细胞肺癌患者及22例健康正常人外周静脉血,应用流式细胞仪检验非小细胞肺癌患者(实验组)与健康人外周血淋巴细胞中(对照组)CD3+、CD4+、CD8+、CD4+4的表达水平。结果实验组与对照组CD3+、CD3+CD4+、CD3+CD8+、CD4+4在淋巴细胞中的比例存在显著性差异(P<0.05),其中,实验组占总淋巴细胞的比例分别为48.07±10.33%、30.93±6.68%、17.13±3.37%、55.45±4.35%;对照组CD3+、CD3+CD4+、CD3+CD8+、CD4+4占总淋巴细胞的比例分别为58.83±10.88%、34.89±6.45%、23.91±4.42%、62.85±7.56%;但鳞癌与腺癌组CD4+4的表达无显著性差异(P>0.05),其中,鳞癌组CD4+4所占比例为61.32±8.06%,腺癌组为64.43±6.76%。结论非小细胞肺癌患者外周血T细胞亚群及CD4+4的表达水平较正常组均低,其表达水平与组织类型无关。     

Decrease in CD4+CD25+ and CD8+CD28+ T cells in interstitial pneumonitis associated with rheumatic disease

The expression of CD25 or CD28 on T cells was examined in patients with rheumatic diseases associated with interstitial pneumonitis (IP), in order to investigate the conditions of CD4⁺CD25⁺ regulatory T cells and CD8⁺CD28⁻ suppressor T cells. Fifty-five patients with various rheumatic diseases and 23 normal controls were enrolled. CD4⁺CD25⁺ T cells of patients with IP were significantly decreased in comparison with non-IP patients, and the ratio of CD8⁺CD28⁻ T cells in patients with IP was significantly higher than that in non-IP patients or normal controls. These results for CD8⁺CD28⁻ T cells were in accord with the decrease in CD8⁺CD28⁺ T cells, and may be related to activation-induced CD8⁺CD28⁺ T-cell death. Thus, the abnormality of CD4⁺CD25⁺ regulatory T cells may be related to the pathogenesis of IP, and the survival and activation of CD8⁺ T cells.     

Decrease in CD4+CD25+ and CD8+CD28+ T cells in interstitial pneumonitis associated with rheumatic disease

Abstract

The expression of CD25 or CD28 on T cells was examined in patients with rheumatic diseases associated with interstitial pneumonitis (IP), in order to investigate the conditions of CD4⁺CD25⁺ regulatory T cells and CD8⁺CD28^? suppressor T cells. Fifty-five patients with various rheumatic diseases and 23 normal controls were enrolled. CD4⁺CD25⁺ T cells of patients with IP were significantly decreased in comparison with non-IP patients, and the ratio of CD8⁺CD28^? T cells in patients with IP was significantly higher than that in non-IP patients or normal controls. These results for CD8⁺CD28^? T cells were in accord with the decrease in CD8⁺CD28⁺ T cells, and may be related to activation-induced CD8⁺CD28⁺ T-cell death. Thus, the abnormality of CD4⁺CD25⁺ regulatory T cells may be related to the pathogenesis of IP, and the survival and activation of CD8⁺ T cells.     

CD19+CD5+ cells as indicators of preeclampsia

Preeclampsia is a devastating pregnancy-associated disorder affecting 5% to 8% of pregnant women worldwide. It emerges as an autoimmune-driven disease, and, among others, the autoantibodies against angiotensin type 1 receptor II have been proposed to account for preeclampsia symptoms. Despite much attention focused on describing autoantibodies associated with preeclampsia, there is no clue concerning the cell population producing them. CD19(+)CD5(+) B-1a B cells constitute the main source of natural and polyreactive antibodies, which can be directed against own structures. Here, we aimed to identify the B-cell subpopulation responsible for autoantibody production during preeclampsia and to study their regulation, as well as their possible use as markers for the disease. The frequency of CD19(+)CD5(+) cells in peripheral blood of preeclamptic patients is dramatically increased compared with normal pregnant women as analyzed by flow cytometry. This seems to be driven by the high human chorionic gonadotropin levels present in the serum and placenta supernatant of preeclamptic patients versus normal pregnant women. Not only ≈95% of CD19(+)CD5(+) cells express the human chorionic gonadotropin receptor, but these cells also expand on human chorionic gonadotropin stimulation in a lymphocyte culture. Most importantly, isolated CD19(+)CD5(+) cells produce autoantibodies against angiotensin type 1 receptor II, and CD19(+)CD5(+) cells were further detected in the placenta of preeclamptic but not of normal pregnancies where barely B cells are present. Our results identify a B-cell population able to produce pregnancy-pathological autoantibodies as possible markers for preeclampsia, which opens vast diagnostic and therapeutic applications.     

CD4+CD25+调节性T细胞与支气管哮喘

支气管哮喘是一种常见的慢性呼吸道疾病,其免疫发病机制尚不十分清楚。CD4 CD25 调节性T细胞是一种特殊的调节性T细胞,参与自身免疫调节,维持自身免疫耐受。本文就CD4 CD25 调节性T细胞的特性及与支气管哮喘的发病机制、治疗、预后的研究进展做一综述。     

CD4+ and CD56+ acute monoblastic leukemia.

We report here a patient with acute monoblastic leukemia whose leukemia cells had CD4 (T4) and CD56 (NKH-1) antigens, in addition to CD36 (OKM5) antigen. The leukemia cells did not have NK or ADCC activities. They showed no rearrangements of immunoglobulin heavy (IgH) chain and T cell receptor (TCR)-beta chain genes, indicating that the leukemia cells were nonlymphoid. The presence of this case suggests that leukemia cells could be originated from monocytes with NK-associated antigen without IgH or TCR rearrangements.     

CD4+ CD56+ Hematodermic Neoplasm Without Cutaneous Involvement

First evidence of cases of haemophilia dates from ancient Egypt, but it was when Queen Victoria from England in the 19th century transmitted this illness to her descendants, when it became known as the “royal disease”. Last decades of the 20th century account for major discoveries that improved the life expectancy and quality of life of these patients. The history and evolution of haemophilia healthcare counts ups and downs. The introduction of prophylactic schemes during the 1970s have proved to be more effective that the classic on-demand replacement of clotting factors, nevertheless many patients managed with frequent plasma transfusions or derived products became infected with the Human Immunodeficiency Virus (HIV) and Hepatitis C virus during the 1980s and 1990s. Recombinant factor VIII inception has decreased the risk of blood borne infections and restored back longer life expectancies. Main concerns for haemophilia healthcare are shifting from the pure clinical aspects to the economic considerations of long-term replacement therapy. Nowadays researchers’ attention has been placed on the future costs and cost-effectiveness of costly long-term treatment. Equity considerations are relevant as well, and alternative options for less affluent countries are under the scope of further research. The aim of this review was to assess the evidence of different treatment options for haemophilia type A over the past four decades, focusing on the most important technological advances that have influenced the natural course of this “royal disease”.