70例免疫性血小板减少症的病原学及治疗分析

目的分析各种致病原对免疫性血小板减少症（ITP）发病的影响。方法对2008年7月至2013年7月在我院儿科收治的70例ITP患儿,分别用被动凝聚法检测肺炎支原体（MP）抗体;免疫荧光法检测呼吸道合胞病毒抗原,腺病毒抗原,流感病毒A、B型,副流感病毒Ⅰ、Ⅱ、Ⅲ型;酶联免疫吸附法（ELISA法）检测EB病毒抗体4项（包括EB病毒早期抗原IgM抗体、EB病毒衣壳抗原IgM抗体、EB病毒衣壳抗原IgG抗体、EB病毒核心抗原IgG抗体）,优生优育抗体[包括弓形虫IgM抗体、风疹病毒IgM抗体、巨细胞病毒（CMV）IgM抗体、单纯疱疹病毒Ⅰ型抗体、单纯病毒Ⅱ型抗体];根据其结果阳性与否给予相应治疗,对发病诱因及转归进行回顾性分析。结果本组CMV-IgM阳性、CMV-DNA阳性19例（27.1%）,MP-Ab阳性14例（20.0%）,呼吸道合胞病毒抗原阳性13例（18.6%）,EA-IgM阳性、VCA-IgM阳性8例（11.4%）,腺病毒抗原阳性6例（8.6%）,副流感病毒Ⅰ、Ⅱ、Ⅲ型阳性6例（8.6%）,流感病毒A、B型阳性4例（5.7%）。治愈42例（60.0%）,良效19例（27.1%）,进步8例（11.4%）,无效1例（1.5%）。加用更昔洛韦治疗的CMV感染者血小板上升比不加用者更为显著,治疗1、2周后的血小板计数恢复更快（P〈0.01）。结论临床医生在治疗ITP时应尽量完善病原学检查,若为阳性应加以相应药物;通过针对病原进行有效合理的治疗,可以缩短病程,减轻患儿家庭经济负担,值得临床推广应用。     

从肝论治治疗复发难治性免疫性血小板减少症对调节T细胞的影响

目的探讨从肝论治治疗复发难治性免疫性血小板减少症对调节T细胞的影响。方法选取复发难治性免疫性血小板减少症患者15例为治疗组,予从肝论治中药汤剂口服;选取15例复发难治性免疫性血小板减少症患者为对照组予强的松片口服,选取健康体检者34例为健康体检组,比较组间治疗前后调节性T细胞比例。结果治疗前治疗组、对照组与健康体检组比较调节T细胞比例有显著差异(P0.01),治疗组与对照组比较无显著差异(P0.01)。治疗后治疗组和对照组患者调节T细胞比例升高,与自身治疗前比较有显著差异(P0.05);治疗后治疗组与对照组比较有显著差异(P0.05)。无明显不良反应发生。结论从肝论治可能通过升高Treg水平从而提升血小板计数,安全有效。     

生物制剂用于成人慢性原发免疫性血小板减少症的治疗进展

原发免疫性血小板减少症(ITP)多以糖皮质激素和(或)静脉注射免疫球蛋白等一线治疗为主,但不少慢性ITP患者需二线或更高级药物治疗,如促血小板生成素受体激动剂、利妥昔单抗或联合药物治疗等.现发现新型药物如fostamatinib、新生儿Fc受体(FcRn)抑制剂及新一代促血小板生成素受体激动剂或对成人慢性ITP有较好的...     

IL-35+调节性B细胞在桥本甲状腺炎免疫发病机制中的作用

目的 探讨IL-35+调节性B细胞(i35-Breg)在桥本甲状腺炎(HT)免疫发病机制中的作用.方法 采用流式细胞术检测36例HT患者及32例对照者外周血CD 19+IL-12p35+IL-27EBI3+细胞比例及PD-L1、CD169、PD-1、CD43、IL-12p35、IL-27EBI3、IL-12Rp2、IL-27Rα、pSTAT1、pSTAT3蛋白表达水平,实时荧光定量PCR检测CD19+细胞SHP-2、Vav mRNA表达,ELISA检测血浆中IL-35、TNF-α、IL-12水平.结果 HT患者外周血CD 19+IL-12p35+IL-27EBI3+细胞比例及IL-12p35、IL-27EBI3、IL-10表达明显低于对照组(P＜0.01).HT患者血浆IL-35水平及CD19+B细胞IL-12Rβ2、IL-27Rα、pSTAT1、pSTAT3表达明显低于对照组(P＜0.01),而血浆TNF-α、IL-12水平及CD14+细胞PD-L1、CD169表达明显高于对照组(P＜0.01).结论 i35-Breg细胞数量及功能异常可能是导致HT患者免疫功能紊乱的重要因素之一.     

B淋巴细胞活化因子在再生障碍性贫血发病中的作用

目的通过检测再生障碍性贫血（aplastic anemia,AA）患者血清中B淋巴细胞活化因子（BAFF）的表达水平,了解BAFF在AA发病机制中的作用。方法采用夹心酶联免疫吸附法测定35例AA患者及22例健康对照者血清BAFF水平并进行比较。结果 AA患者血清BAFF水平（中位数1 134 ng/L,299~6 886 ng/L）与健康对照组（中位数1 375 ng/L,762~1 947 ng/L）比较差异无统计学意义（P〉0.05）。结论 BAFF在AA的发病中可能未发挥直接作用,但BAFF可能通过其他途径间接参与了AA的发病。     

健脾益气摄血颗粒对脾气虚型慢性免疫性血小板减少症淋巴细胞亚群的影响

目的 探讨健脾益气摄血颗粒对脾气虚型慢性免疫性血小板减少症淋巴细胞亚群的影响。方法 符合入选病例标准的慢性免疫性血小板减少症（CITP）门诊及住院患者 40例,随机分为健脾益气摄血联合强的松治疗组、单用强的松为对照组,分别给予健脾益气摄血配方颗粒联合强的松及单用强的松治疗,各组疗程均为21 d,比较2组患者治疗前后其外周血CD₁₉⁺细胞表达及T淋巴细胞亚群变化。结果（1）中医证候疗效比较：治疗组及对照组总有效率分别为75%（15/20）、40%（8/20）,二组比较差异有统计学意义（P<0.05）;其中治疗组中医证候疗效优于对照组,差异有统计学意义（P<0.05）;（2）CD₁₉⁺B细胞表达比较：对照组患者CD₁₉⁺CD₂₇⁺及CD₁₉⁺CD₂₇^-B细胞表达治疗前后比较差异无统计学意义（P>0.05）,治疗组治疗前后及与对照组治疗后比较差异有统计学意义（P<0.05）。其中治疗组CD₁₉⁺细胞比例低于对照组;（3）T细胞亚群变化比较：治疗组患者血清CD₄⁺百分率较治疗前以及对照组均显著降低,而CD₈⁺百分率则升高,CD₄⁺/CD₈⁺比例显著减小（P<0.05）。结论 健脾益气摄血颗粒能提高脾气虚型慢性免疫性血小板减少症中医症候临床疗效,对体液免疫及细胞免疫具有调节作用。     

细胞因子及炎症指标在发热伴血小板减少综合征与脓毒症合并血小板减少症鉴别诊断中的意义

目的:对比分析发热伴血小板减少综合征(SFTS)与脓毒症合并血小板减少症患者入院时细胞因子、血常规、C-反应蛋白(CRP)、降钙素原(PCT)等指标水平的差异,为两者早期鉴别诊断提供实验室依据.方法:收集SFTS患者34例(A组)、脓毒症合并血小板减少症患者39例(B组)的临床资料,回顾性分析2组患者入院时炎症指标水平的差异,并绘制受试者工作特性曲线(ROC曲线).结果:①A组白细胞计数(WBC)和中性粒细胞计数(NEUT)明显低于B组(P＜0.05);A组血小板计数(PLT)明显低于B组(P＜0.05),且2组PLT均低于正常范围;B组纤维蛋白原(FIB)明显高于A组(P＜0.05).②B组PCT、CRP均明显高于A组(P＜0.05),且A组PCT仅个别病例升高;B组中性粒细胞与淋巴细胞比值(NLR)、红细胞分布宽度(RDW)均明显高于A组(P＜0.05);2组患者白细胞介素-6(IL-6)、肿瘤坏死因子α(TNF-α)、D二聚体(D-D)均升高,2组之间差异无统计学意义(P＞0.05);2组患者淋巴细胞计数(LYMPH)差异无统计学意义(P＞0.05).③ROC曲线分析显示,SFTS患者WBC、NEUT、PCT、CRP、NLR的ROC曲线下面积(AUC)＞0.9.结论:在SFTS与脓毒症合并血小板减少症发病初期,患者血液中PCT、CRP、WBC、NEUT、PLT、NLR、RDW、FIB水平存在差异,且WBC、NEUT、PCT、CRP、NLR对两者具有较高的诊断价值.     

肌醇脂质和cAMP在血小板活化因子诱导血小板聚集中的作用

目的：探讨肌醇脂质和cAMP两个细胞内第二信使系统在血小板活化因子(PAF)诱导血小板聚集过程中所起到的作用和相互关系。方法：采用PKC激动剂PMA和Ca^2 通道A23187,以及PKA激动剂Sp-cAMPS和抑制剂Rp-cAMPS干预的方法,分析观察这两个信使系统在PAF诱导血小板聚集过程中的作用;采用^3H—Inositol和^14C-Adenine双标记液体闪烁技术测定PAF诱导血小板可逆聚集过程中肌醇-1,4,5-三磷酸酯(IP3)和cAMP的水平变化的方法,分析研究这两个信使系统在PAF诱导血小板聚集过程中的相互关系。结果：(1)PMA和A23187能分别增强PAF的血小板聚集效应,而且两者具有协同作用;(2)Rp-cAMP和Sp-cAMPS两者本身都不能引起血小板聚集,但能分别增强和抑制PAF的聚集效应;(3)IP3和cAMP的水平变化分别与血小板的聚集和解聚过程一致。结论：(1)肌醇脂质信使系统是细胞内转导PAF诱导血小板聚集的主要胞内信使系统。(2)降低血小板内cAMP浓度不能诱导聚集,但能增强肌醇脂质信使系统的聚集效应;升高cAMP水平能拮抗肌醇脂质信使系统的作用,这可能是使可逆相聚集的血小板解聚的一个重要机制。     

中华鲟B细胞活化因子的分子表征及与免疫反应相关的潜在功能

[目的]探究中华鲟B细胞活化因子(CsBAFF)的分子表征及其与免疫反应相关的潜在功能.[方法]通过免疫刺激后获得中华鲟各组织.结合生物信息学分析,构建和筛选CsBAFF的cDNA文库,并采用定量RT-PCR进行验证分析.采用分子生物学的方法进行CsBAFF的质粒构建及重组sCsBAFF的制备.采用MTT试验检测细胞的增殖,以及结合免疫印迹分析相关蛋白的表达.[结果]克隆了CsBAFF的cDNA,包含765个核苷酸的开放阅读框,编码255个氨基酸,分子量为28.9 kD.CsBAFF具有跨膜结构域、TNF结构域、furin蛋白酶裂解位点、长D-E环、1个潜在的N-连接糖基化位点和2个保守的半胱氨酸残基.CsBAFF基因主要表达于头肾和脾脏,且三价灭活疫苗和聚肌苷酸均能诱导CsBAFF基因表达.重组CsBAFF能促进中华鲟和小鼠淋巴细胞的增殖,其中保守的半胱氨酸残基Cys201和Cys214是CsBAFF发挥生理功能必不可少的位点.[结论]B细胞活化因子(BAFF)是肿瘤坏死因子(TNF)家族成员之一,在B淋巴细胞的增殖、存活、分化和成熟过程中起着重要作用.     

Stability of the regulatory T cell lineage in vivo

Tissue maintenance and homeostasis can be achieved through the replacement of dying cells by differentiating precursors or self-renewal of terminally differentiated cells or relies heavily on cellular longevity in poorly regenerating tissues. Regulatory T cells (T(reg) cells) represent an actively dividing cell population with critical function in suppression of lethal immune-mediated inflammation. The plasticity of T(reg) cells has been actively debated because it could factor importantly in protective immunity or autoimmunity. By using inducible labeling and tracking of T(reg) cell fate in vivo, or transfers of highly purified T(reg) cells, we have demonstrated notable stability of this cell population under physiologic and inflammatory conditions. Our results suggest that self-renewal of mature T(reg) cells serves as a major mechanism of maintenance of the T(reg) cell lineage in adult mice.     

The influence of allogeneic cells on the human T and B cell repertoire

Clinical transplantation is often complicated by rejection episodes, in which the immune system of the recipient reacts to the foreign transplantation (HLA) antigens on the graft. This immune response includes humoral and cellular components. In the first, B lymphocytes form antibodies to the HLA alloantigens. In the second, CD8+ T lymphocytes recognize and react to HLA class I antigens, and CD4+ T cells react to HLA class II antigens. The frequency and severity of these rejection episodes can be diminished by immunosuppressive drugs, HLA matching between donor and recipient, and immune modulation by blood transfusion. Effective HLA matching between donor and recipient is not always possible and often not necessary. Insight into the factors that influence the T and B cell repertoire after blood transfusion might lead to new approaches to improve graft survival.     

Emerging challenges in regulatory T cell function and biology

Much progress has been made in understanding how the immune system is regulated, with a great deal of recent interest in naturally occurring CD4+ regulatory T cells that actively engage in the maintenance of immunological self-tolerance and immune homeostasis. The challenge ahead for immunologists is the further elucidation of the molecular and cellular processes that govern the development and function of these cells. From this, exciting possibilities are emerging for the manipulation of regulatory T cell pathways in treating immunological diseases and suppressing or augmenting physiological immune responses.     

Lymphotoxin is an important T cell-derived growth factor for human B cells

Two different assays for B cell growth factors (BCGF) and an antibody against lymphotoxin were used to show that the presence of lymphotoxin in conditioned media derived from normal activated T cells and in a partially purified BCGF accounts for a substantial portion of their B cell growth-promoting activity. A competitive binding assay confirmed the presence of significant amounts of lymphotoxin in the partially purified BCGF. Recombinant lymphotoxin enhanced the proliferation of activated B cells and augmented B cell proliferation and immunoglobulin secretion induced by interleukin-2.     

HCV persistence and immune evasion in the absence of memory T cell help

Spontaneous resolution of hepatitis C virus (HCV) infection in humans usually affords long-term immunity to persistent viremia and associated liver diseases. Here, we report that memory CD4+ Tcells are essential for this protection. Antibody-mediated depletion of CD4+ Tcells before reinfection of two immune chimpanzees resulted in persistent, low-level viremia despite functional intra-hepatic memory CD8+ Tcell responses. Incomplete control of HCV replication by memory CD8+ Tcells in the absence of adequate CD4+ Tcell help was associated with emergence of viral escape mutations in class I major histocompatibility complex-restricted epitopes and failure to resolve HCV infection.     

T cell-independent rescue of B lymphocytes from peripheral immune tolerance

Autoimmunity arises when immune tolerance to specific self-antigens is broken. The mechanisms leading to such a failure remain poorly understood. One hypothesis proposes that infectious agents or antigens can break B or T lymphocyte self-tolerance by expressing epitopes that mimic self. Using a transgenic immunoglobulin model, we show that challenge with self-mimicking foreign antigen rescues B cells from peripheral tolerance independent of T cell help, resulting in the accumulation of self-reactive cells in the lymph nodes and secretion of immunoglobulins that bind to a liver-expressed self-antigen. Therefore, our studies reveal a potentially important mechanism by which B lymphocytes can escape self-tolerance.