急性免疫性血小板减少症患儿血清IL-33检测及其意义

为研究IL-33在儿童急性免疫性血小板减少症(ITP)发病机制中的作用及意义,我们采用ELISA法检测了37名ITP患儿和37名对照者血清IL-33水平,分析IL-33与患儿就诊时血小板计数及后期疗效的关系。我们发现,ITP患儿血清IL-33较对照者明显增高(P<0.01),且与血小板计数呈负相关(R2=0.10,P=0.05)。血清IL-33水平与治疗效果密切相关,采用IL-33预测ITP患儿疗效,预测敏感性为0.88,特异性为0.81。这些结果提示:IL-33参与了ITP的发病机制,血清IL-33水平可以作为预测患儿疗效的免疫学指标。     

免疫性血小板减少症患儿外周血Treg细胞GITR表达及临床意义

目的：探讨免疫性血小板减少症(ITP)患儿外周血Treg细胞GITR表达,以及GITR表达与淋巴细胞亚群、炎症因子、ITP病程的相关性。方法：下载GSE23754数据集(来自GEO数据库),GSEA分析ITP患儿外周血GITR mRNA水平与细胞免疫相关信号通路的相关性。收集华中科技大学同济医学院附属武汉儿童医院2020年12月至2021年2月新确诊的ITP患儿(n=34)和同期健康体检儿童(n=46)外周血,qPCR检测外周血单个核细胞(PBMC)GITR mRNA表达;CBA法检测外周血血清中炎症因子水平;流式细胞术分析外周血淋巴细胞亚群和T细胞GITR表达。结果：GSE23754数据集GSEA分析结果显示,ITP患儿GITR mRNA表达与效应T细胞功能信号通路呈负相关(NES=-1.30,P=0.035)。Pearson相关分析结果显示,新确诊ITP患儿PBMC的GITR mRNA表达与外周血CD8⁺T细胞数及IL-2、TNF-α水平呈负相关(均P<0.05)。流式细胞术结果显示,GITR主要在儿童外周血Treg细胞表面表达,且ITP患儿Treg细胞...     

万古霉素可诱导免疫性血小板减少症

美国血液研究所的Richard H．Aster博士及其同事在3月1日的《新英格兰医学杂志》（N Engl J Med，2007；356：904—910．）上报告，糖肽抗生素万古霉素可引起中性粒细胞减少症。研究者总结说，检测药物依赖性抗体有助于确定接受万古霉素患者血小板减少症的原因。     

rituximab有望治疗儿童免疫性血小板减少症

抗CD20单克隆抗体rituximab在儿童身上表现出了抗慢性免疫性血小板减少症(ITP)的活性。     

射频消融治疗顽固性免疫性血小板减少症

目的探讨脾脏射频消融术治疗顽固性免疫性血小板减少症（ITP）的安全性和有效性。方法回顾分析我院开展的国际首例脾脏射频消融治疗ITP的疗效。结果 1例43岁女性食管癌患者,经反复外周血计数、血涂片和骨髓穿刺等检查证实合并原发性重症ITP,其血小板计数小于（5~10）×109/L,经规范抗幽门螺旋杆菌治疗、静滴人免疫球蛋白、甲基强的松龙、长春新碱和输注血小板等治疗无效。患者接受腹腔镜下脾脏射频消融术治疗,术后第22天血小板计数恢复正常,无围手术期并发症;随访超过8个月,患者呈完全应答。结论脾脏射频消融术治疗顽固性ITP安全、有效,值得扩大临床试验进一步验证其疗效。     

原发性免疫性血小板减少症的诊治研究进展

原发性免疫性血小板减少症(ITP),常见发病人群为儿童,是一种出血性自身免疫性疾病.该疾病特点为皮肤黏膜瘀点、瘀斑,血象显示外周血血小板计数减少,巨核细胞数或正常或增多,但可见巨核细胞发育、成熟障碍.目前ITP发病机制未明,涉及体液免疫、细胞免疫及细胞因子等诸多方面,其治疗分一线、二线及其他手段.     

免疫性血小板减少症患者外周血Treg 细胞microRNA 分析

目的:分析ITP 患者和健康对照组Treg 细胞中miRNA 的表达谱的差异,探讨ITP 的发病机制。方法:抽取ITP 患者组和健康对照组外周静脉血,应用流式细胞仪分选Treg 细胞,提取每组患者Treg 细胞中的RNA,采用Solexa 深度测序法对其miRNA 表达谱进行分析。对比ITP 组和正常对照组芯片结果,找出差异表达的miRNA,并对其进行富集性分析,找寻异常信号通路。结果:我们筛查到ITP 患者组Treg 细胞中存在多个miRNA 表达异常,其中有显著差异者为miR-1976, miR-548ae-5p、miR-5096-p3、miR-548am-5p、PC-3p-63471、PC-3p-96627。通过富集性分析发现ErbB 和TGF鄄茁两个异常信号通路。结论:ITP 患者外周血Treg 细胞内miRNA 表达谱存在差异表达,这些差异表达的miRNA 可能影响了Treg 细胞发挥正常的免疫调节功能,是ITP 发生的机制之一。     

急性免疫性血小板减少动物模型的实验研究

目的：制备急性免疫性血小板减少动物模型。方法：采用洗涤小鼠血小板免疫家兔获得抗小鼠血小板血清（APS）;将74只BALB／c小鼠随机分为3组：对照组（10只）、APS组（32只）、正常家兔血清（NRS）组（32只）。对照组经尾静脉注射灭菌生理盐水100ul,APS组经尾静脉注射1：4浓度抗小鼠血小板血清APS100ul,NRS组经尾静脉注射正常家兔血清100ul。每组均于注射前和注射后第3、6、12小时取小鼠尾静脉血,进行血小板。白细胞及红细胞计数,并测定每个时间点断尾出血时间。结果：APS组外周血象显示各时间点血小板计数进行性减少,出血时间进行性延长,第3、6、12小时所测血小板计数值与NRS组及对照组比较亦差异显著（p〈0．01）,而红细胞和白细胞计数无显著变化（p〉0．05）。NRS组、对照组各时间点及组间血小板计数、出血时间、白细胞计数、红细胞计数均无显著差异。结论：用免疫血清法制备急性免疫性血小板减少模型方法可行,可靠,成功率高。     

假性血小板减少症分析前的质量控制

假性血小板减少症（pseudothrombocytopenia,PTCP）是由于在EDTA（枸橼酸盐、肝素等）作为抗凝剂的前提下出现的免疫介导的血液中冷抗血小板自身抗体,使血小板互相聚集现象,这种EDTA依赖的冷抗血小板自身抗体直接作用于血小板膜糖蛋白Ⅱb/Ⅲa上,同时,这种与血小板结合的自身抗体Fc端可与单核细胞或淋巴细胞膜上Fc受体结合,     

Functional mapping of the Fc gamma RII binding site on human IgG1 by synthetic peptides

Receptors specific for the Fc part of IgG (Fc gamma R) are expressed by several cell types and play diverse roles in immune responses. Impaired function of the activating and inhibitory Fc gamma R may result in autoimmunity. Thus, the modulation of IgG-Fc gamma R interaction can be a target for the development of treatments for some autoimmune and inflammatory diseases. This study addresses the localization and functional characterization of linear sequences in human IgG1 which bind to Fc gamma RII. Peptides with overlapping sequences derived from the CH2 domain of human IgG1 between P(234) and S(298) were synthesized and used in binding and functional experiments. Binding of the peptides to Fc gamma R was assayed in vitro and ex vivo, and peptides found to interact were functionally tested. The shortest effective peptide was T(256)-P(271), which bound to soluble recombinant Fc gamma RIIb with K(d)=6 x 10(6) M(-1). The biotinylated peptides R(255)-P(271) and T(256)-P(271) complexed by avidin exhibited functional activity; they induced Fc gamma RIIb-mediated inhibition of the BCR-triggered Ca(2+) response of human Burkitt lymphoma cells, and inflammatory cytokine production (TNF-alpha and IL-6) by the human monocyte cell line MonoMac. In conclusion, our results suggest that the selected peptides functionally represent the Fc gamma RII-binding part of IgG1.     

Highly reduced binding to high and low affinity mouse Fc gamma receptors by L234A/L235A and N297A Fc mutations engineered into mouse IgG2a

The effects of the Fc silencing mutations such as leucine (L) to alanine (A) substitution at the position 234 and 235 (LALA) and the alanine (A) to asparagine (N) substitution at position 297 (N297A) are well investigated for human IgG. However, the effects of the same two silencing Fc mutations in a mouse IgG backbone are not yet well investigated in respect to binding to mouse Fc gamma receptors (FcγRs), complement and subsequent effector functions. By using a mouse IgG2a tool antibody directed against mouse OX40L, we demonstrate a strongly reduced binding of the two Fc mutants to high and low affinity recombinant and cell expressed mouse FcγRs, when compared to the mouse IgG2a with the wild type (wt) backbone. Reduced FcγR binding by the two investigated Fc mutants could further be confirmed on primary mouse macrophages expressing their native FcγRs. In addition, we reveal that the LALA and N297A mutations in the mIgG2a also slightly reduced binding to C1q of human origin. Thus, here we provide experimental evidence that the two investigated Fc mutations in the mouse IgG backbone lead to similar “silencing” properties as previously demonstrated for the human IgG and thus represent a useful method to alter effector functions in tool antibodies to be used in mouse models.     

FcεRⅡ／CD23在支气管哮喘发病中作用的研究

本文以急性发作期病人和缓解期病人及正常人各２０例为研究对象，探讨ＩＬ－４－ＦｃεＲⅡ／ＣＤ２３－ＩｇＥ在支气管哮喘中的调节作用。结果表明，急性发作期病人的ＩＬ－４分泌细胞、ＦｃεＲⅡ／ＣＤ２３阳性淋巴细胞和血清总ＩｇＥ水平均明显高于缓解期病人和正常对照组。在急性发作时，ＩＬ－４和ＣＤ２３之间存在着正相关。进一步表明病人体内ＩＬ－４水平升高可以诱导淋巴细胞表面ＦｃεＲⅡ／ＣＤ２３分子表达的增强，并在ＩｇＥ抗体形成中起着重要作用。     

FcγRⅡb基因多态性与常见风湿病发病相关性研究进展

FcγRⅡb属FcγR中的抑制性受体,编码基因位于染色体1 q23.多项研究认为其基因多态性与系统性红斑狼疮(systemic lupus erythematosus,SLE),类风湿关节炎(rheumatoid arthritis,RA),强直性脊柱炎(ankylosing spondylitis,AS)等风湿免疫病相关.而在不同种族的人群中研究结果不同,但仍可以认为,FcγRⅡb基因多态性在某些人群的常见风湿免疫病发病过程中起重要作用.

Abstract：

IgG Fc receptor Ⅱ b ( FcγR Ⅱ b ) is an inhibitory Fc receptor expressed on B cells and myeloid cells, and its coding gene is located on Chromsome 1 q23. These receptors are very important for the regulation of body' s responses to infection. The reduced expression of function of these receptors may predispose to autoimmunity. The FcγR Ⅱ b gene polymorphisms affect the affinity with which FcRs interact with immunoglobulin molecules. Correlation of the FcγR Ⅱ b polymorphisma with susceptibility of common rheumatic diseases, such as Systemic Lupus Erythematosus ( SLE ) , Rheumatoid Arthritis ( RA ) ,Ankylosing Spondylitis (AS) , has been reported in various populations, but the results were inconsistent.     

Fc receptors in antibody-dependent enhancement of viral infections

Sensitization of the humoral immune response to invading viruses and production of antiviral antibodies forms part of the host antiviral repertoire. Paradoxically, for a number of viral pathogens, under certain conditions, antibodies provide an attractive means of enhanced virus entry and replication in a number of cell types. Known as antibody-dependent enhancement (ADE) of infection, the phenomenon occurs when virus-antibody immunocomplexes interact with cells bearing complement or Fc receptors, promoting internalization of the virus and increasing infection. Frequently associated with exacerbation of viral disease, ADE of infection presents a major obstacle to the prevention of viral disease by vaccination and is thought to be partly responsible for the adverse effects of novel antiviral therapeutics such as intravenous immunoglobulins. There is a growing body of work examining the intracellular signaling pathways and epitopes responsible for mediating ADE, with a view to aiding rational design of antiviral strategies. With in vitro studies also confirming ADE as a feature of infection for a growing number of viruses, challenges remain in understanding the multilayered molecular mechanisms of ADE and its effect on viral pathogenesis.     

Requirement of the Fc receptor common gamma-chain for gamma delta T cell-mediated promotion of murine experimental autoimmune encephalomyelitis

Immunoglobulin Fcgamma receptors (FcgammaR) are comprised of a ligand-binding alpha-chain that sometimes associates with a cell signaling common gamma-chain. These receptors comprise an important family of effector molecules that link humoral and cell-mediated adaptive immunity and regulate innate immunity. Recent animal studies suggest that FcgammaR in general, and FcR alpha-chains in particular, are required for full development of experimental autoimmune encephalomyelitis (EAE). We show here that deletion of the gamma-chain renders mice resistant to EAE, whereas deletion of the alpha-chains of FcgammaRI, FcgammaRIIB and FcgammaRIII has no protective effect. Susceptibility to EAE is fully restored in common gamma-chain-/- mice into which wild-type splenocytes are adoptively transferred, but EAE is not restored in common gamma-chain-/- mice given wild-type splenocytes depleted of gammadelta T cells. These data indicate that although the common gamma-chain is required for full development of EAE in mice, this requirement is likely FcgammaR alpha-chain-independent. Expression of the common gamma-chain by gammadelta T cells, probably in conjunction with the T cell receptor/CD3 complex, is likely the key requirement for full development of EAE.     

Fc receptors are major mediators of antibody based inflammation in autoimmunity

There is now renewed interest in the role of antibodies in autoimmunity. Recent compelling evidence indicates that autoantibodies and the effector mechanisms they induce, for example, Fc receptor activation of leukocytes and/or the complement cascade, are central players in the development of autoimmunity, by perpetuating inflammation and perhaps even regulating the process itself. Of increasing interest are Fc receptors, which have been more closely investigated in the past decade using recombinant proteins, gene deficient mice and mouse models of human disease. These analyses point towards major roles of Fc receptors in antibody hypersensitivity reactions and by extension autoimmune disease, and they reveal opportunities in the development of novel therapeutic approaches in the treatment of autoimmune diseases.     

Ethnic variation of Fc gamma receptor polymorphism in Sami and Norwegian populations

Receptors for the Fc domain of IgG (Fc gammaR) play a critical role in linking cellular and humoral immunity. The various Fc gammaR genotypes may contribute to differences in infectious and immune-related diseases in various ethnic populations. The Samis are the aboriginal inhabitants of Norway and Fennoscandinavia and differ ethnically from the Norwegians. The distribution of various immune-related diseases has been reported to differ between Sami and Norwegians. This is the first study to evaluate the distribution of Fc gammaR polymorphisms in a Sami population. Two hundred Samis were genotyped for polymorphisms in the Fc gammaRIIA, Fc gammaRIIIA and Fc gammaRIIIB genes. The genotype and allele frequencies were compared with those of 272 healthy Norwegians. The Sami and Norwegian Fc gammaRIIA, Fc gammaRIIIA and Fc gammaRIIIB genotypes differed significantly. The Samis had higher frequencies of the Fc gammaRIIa-H/H131, Fc gammaRIIIa-F/F158 and Fc gammaRIIIb-NA1/NA1 genotypes. The Fc gammaR genotypes were non-randomly distributed in both populations. These findings may be important for the prevalence of autoimmune and infectious diseases in the two populations.     

Modulation of human peripheral blood lymphocyte Fc gamma receptors by immune complexes: recovery of Fc gamma receptors in the presence of normal human serum.

When normal human peripheral blood lymphocytes (PBL) were incubated at 37 degrees with soluble transferrin anti-transferrin (TAT) complexes a significant reduction in the proportion of PBL bearing receptors for the reacted Fc portion of IgG(Fc gamma R) was found. Following incubation of such complex-treated PBL in normal human serum the proportion of Fc gamma R + PBL, as assessed by rosette formation with chicken erythrocytes (E) presensitized with rabbit antibody (A) was found to be significantly increased. Such serum-mediated recovery of Fc gamma R was not affected by pretreating PBL with cycloheximide. Recovery was found to be species restricted, Ca++ dependent and confined to a serum fraction containing molecules of relatively low molecular weight (less than 90,000 Mr). Following absorption with EA the restorative capacity of human serum was lost. These findings suggest that following modulation of human PBL-Fc gamma R by immune complexes, receptors may be restored to the cell surface from a serum pool of 'fluid-phase' Fc gamma R. The origin and biological significance of serum Fc gamma R is not known but it is conceivable that they play an important role in immunoregulation.     

Characterization of Fc epsilon RI gamma in human natural killer cells.

We report the characterization of the Fc epsilon RI gamma chain which associates with the transmembrane form of CD16 to form the low affinity receptor for IgG (Fc gamma RIII) expressed on human natural killer (NK) cells. cDNA cloning and sequence analysis of Fc epsilon RI gamma from a polyclonal CD3-CD16+ NK line established that this molecule is identical to Fc epsilon RI gamma previously identified in human basophils as part of a high affinity receptor for IgE. Polymerase chain reaction analysis of Fc epsilon RI gamma gene expression in a series of CD3+CD16- and CD3-CD16+ NK clones reveals that Fc epsilon RI gamma is not directly linked to NK activity since clones of the CD3+CD16- phenotype lack Fc epsilon RI gamma RNA but nevertheless mediate cytotoxicity. Taken together, these results demonstrate that the Fc epsilon RI gamma molecule is expressed in various types within the hematopoietic system as part of multimeric surface receptors involved in different biological functions.