摘要
研究背景：
过敏性紫癜(Henoch Scholein Purpura, HSP)是儿童时期最常见的自身免疫性小血管炎性疾病,病因及发病机制至今未明。主要发生在5-15岁儿童及青少年群体,成人及婴幼儿相对而言少见。非血小板减少性紫癜是该病的主要特点。该病还可能累及关节、胃肠道、肾脏,大脑、肺脏,阴囊等。感染、疫苗接种、药物、食物等可能是该病的诱发因素。虽然HSP被认为是一种自限性疾病,但因累及器官较多,可造成患儿迁延不愈,特别是肾脏的累及,有可能导致患儿终生就医。有些患者甚至发展为功能衰竭,在很大程度上影响着其治愈程度以及后期的生活质量。发病患者中有1/3还可能会复发,而肾脏的累及则是导致疾病复发及迁延不愈的主要原因之一。因此,充分了解HSP的发病机制,从根本上治疗该疾病,提高患儿的生活质量,不但是临床工作者亟待解决的问题,也是小儿免疫性疾病领域一直渴望攻克的难关。近年来,相关学者利用先进的生物学技术,从分子、基因等层面去分析探讨HSP的发病机制,并且结合大量相关的流行病学调查资料,探索并寻求有效的治疗途径,虽然也取得了相应的成果,但是对于HSP发病机制、诊疗措施等方面依然有很多问题有待探究,有待解决,这些问题的解决对HSP疾病的诊疗及预后具有重要意义。
目前相关研究表明该病的发病与机体免疫功能异常有关,包括T淋巴细胞功能失调、体液免疫紊乱和细胞因子分泌异常。炎症机制、凝血与纤溶机制和基因易感性等也可能参与其发病。小血管周围多形核细胞、淋巴细胞和嗜酸性细胞浸润,小血管壁IgA复合物、补体及其他免疫复合物沉积是HSP的基本病理特征。HSP患者急性期血清IgA水平升高及某些非特异性的前性因子,如肿瘤坏死因子(tumor necrosis factor,TNF)-α、白介素6(interleukin-6, IL-6)等增加,暗示着炎症、免疫紊乱及自身免疫耐受被打破在HSP发病及进展过程中,发挥着极为重要的作用。Sugiyama等曾报道切除扁桃体并应用强的松成功治疗了HSP引发的紫癜性肾炎。Someya T等曾报道对甾类激索耐药的HSP患者应用免疫抑制剂可以有效缓解病情。越来越多的研究结果表明免疫调节可以降低HSP局部炎症扩散,延缓病情发展。
B细胞多克隆活化产生相应抗体,加重疾病的炎症反应是多年来公认的HSP典型的免疫紊乱特点。但是T细胞功能异常和细胞因了比例失调越来越受到了关注,相关报道表明CD4+T细胞各亚矿群比例失调和功能紊乱可能是HSP免疫失耐受的重要原因。
辅助性T细胞17(T helper cells17, Th17cells)是新近发现的不同于辅助性T细胞1(T helper cells1,Th1cells)和辅助性T细胞2(T helper cells1,Th2cells)的辅助性T细胞(T helper, Th)亚群,定义为表达白介素17(interleukin-17, IL-17)的CD4+T细胞,转化生长因子-β (transforming growth factor-β,TGF-β)和IL-6是Th17细胞分化所必需的细胞因子,而白介索23(interleukin-23, IL-23)对Th17的扩增及维持起到重要作用。Th17细胞在自身免疫性疾病和慢性炎症的发病、发展、转归过程中有非常重要的作用。目前,在各种自身免疫性疾病,包括类风温性关节炎、多发性硬化、系统性红斑狼疮、以及哮喘等患者的血清及组织中检测到了IL-17的高表达。同时，IL-17缺陷小鼠或用IL-17受体拮抗剂处理的小鼠表现出对佐剂诱导的关节炎、或实验性自身免疫性脑脊髓膜炎(Experimental autoimmune cerebrospinal meningitis, BAE)的抵抗。,以上结果提示,IL-17参与了人或动物多种自身免疫性疾病的发病过程。而Th17细胞与HSP的发病机制之间的关系,也成为了相关研究者关注的焦点。许多研究表明HSP急性期患儿存在Th17细胞活化现象,提示Th17细胞参与了HSP的发病过程。Li YY等曾报道与健康儿童相比,HSP急性期患儿外国血Th17细胞、Th2细胞比例显著增高，推断Th17细胞与HSP的发病密切相关。Jen HY等最近也做了相关的研究,研究结果表明HSP急性期患儿外周血Th17细胞比例升高,IL-17水平显著升高,Th17细胞有可能参与了HSP的炎症反应过程。杨军等曾报道HSP急性期患儿Th17细胞特异性转录因子维甲酸受体相关孤独核受体(Retinoid-related orphan nuclear receptor-γ t,ROR-γ t)表达明显增加,提示Th17细胞过度活化。白介素18(interleukin-18, IL-18)是一种新近发现的前炎性因子,其可以促进IL-6和白介素8(interleukin-8, IL-8)的分泌,而IL-6和IL-8与IL-17的分泌、Th17细胞的分化以及HSP的发病密切相关。
机体中对相关炎症及免疫反应能够起到抑制及调节作用的细胞很多,如树突状细胞、B细胞及CD4+CD25+调节性T细胞(T regulatory cells,Treg)等,而Treg细胞的调节作用尤为显著。Treg细胞对机体自身抗原的免疫耐受及抑制相应免疫反应过度活化方面起到了十分重要的作用。又头翼状旋转转录因子3(Forkhead-winged helix transcription factor3, Foxp3)基因是其特异性标志,对Treg细胞的活化及功能调节方面起到了至关重要的作用。有报道表明缺乏Foxp3基因的小鼠模型可以发生致命的炎症反应,而该炎症反应可以通过移植Treg细胞将其控制。Treg细胞调节机体免疫反应的机制很多,如它可以竞争性的聚集在树突状细胞周围,从而抑制效应细胞的增殖及活化。炎症及免疫反应发生时,Treg细胞可以聚集于损伤组织局部发挥相应功能。我国学者近期发现Treg细胞在HSP中同样存在数量和功能的异常。王强等报道HSP急性期患儿外周血Treg细胞比例降低。杨军等也有过类似的报道,他们发现HSP急性期患儿外周血Treg细胞比例明显低于健康儿童。但LiYY等的报道结果与之不同,其研究结果显示与健康儿童相比,HSP急性期患儿外周血Treg细胞比例未见明显差异。
综上所述,虽然Ireg细胞和Th17细胞都是CD4+T细胞来源的Th亚群,但在HSP中却可能存在二者失衡的情况。该失衡情况是否与HSP的发病相关,以及该失衡与疾病重程度是否相关,该关衡是否可以作为检测指标反应HSP的疾病严重程度,解决以上问题对于探讨HSP的发病机制,寻求有效的治疗途径具有重要意义。
T细胞免疫球蛋白粘蛋白分子-3(T cell immunoglobulin-and mucin domain-containing molecules,Tim-3)是新近发现的具有调节T细胞功能的分子。该分子通过与其配体半乳糖凝集素-9(Galectin-9)结合发挥相应作用,可以下调Thl细胞及Th17细胞反应,在免疫反应及炎症反应中发挥重要作用。在非肥胖型糖尿病,EAE等Thl型应答占优势的自身免疫性疾病的患者和动物模型中已经检测出Tim-3, Galectin-9, T-bet转录因子(T-box expressed in T cells, T-bet)等因子mRNA和蛋白质的表达失衡。Tim-3在CD4+T细胞上的表达变化也是近几年关注的热点。Jones等曾报道在人类免疫缺陷病毒感染的患者CD4+T细胞上Tim-3表达上调。Ying L等也报道风湿性关节炎急性期患者CD4+T细胞Tim-3表达上调。目前,通过激活Tim-3/Galectin-9通路下调Th17细胞的作用已成为自身免疫性疾病相关研究的重要着眼点。
近年来,Tim-3/Th17/Treg关联轴与HSP发病的联系正日益受到关注。国内外已有应用细胞因子或受体拮抗蛋白进行相关治疗的研究报道,但由于单一细胞因子在缓解症状和治疗效果方面十分有限,因此针对参与疾病的发生、发展的上游因子的治疗已成为当前靶向治疗的新趋势。
本研究以Th17, Treg, Tim-3等细胞因r为指标,从细胞和分子水平探讨Th17/Treg体系及Tim-3在HSP的发生和发展中的作用。本研究结果将为揭示HSP患者免疫紊乱及细胞因子紊乱形成的原因提供新的思路,同时也为HSP的治疗提供新的见解及策略。
目的：明确HSP急性期患儿体内外周血Th17/Treg的平衡情况,以及该平衡情况.与患儿临床表现和部分实验室检查的相关性,探讨Th17/Treg失衡在HSP发病过程中的作胜及临床意义。
方法：选取23名HSP急性期患儿及18名健康对照作为研究对象,流式细胞分析术检测Th17细胞、Treg细胞在各组研究对象外周血中的表达及比例变化。酶联免疫吸附法检测各组研究对象血清中IL-17、IL-10、IL-18等的水平。分析HSP急发型期患儿体内Th17/Treg的平衡变化,并结合相关临床表现及实验室检查,分析Th17/Treg的关衡状况与HSP急性期患儿的发病及临床表现的关系。
结果：1、与健康对照组相比,HSP急期患儿外周血Th17细胞比例升高。
2、与健康对照组相比,HSP急性期患儿外周血CD3+CD8-IL-21+T细胞比例升高。
3、与健康对照组相比,HSP急性期患儿外周血Treg细胞比例降低。
4、与健康对照组相比,HSP急性期患儿外周血Th17/Treg比例升高。
5、与健康对照组相比,HSP急性期患儿血清中IL-17水平显著增高。
6、与健康对照组相比,HSP急性期患儿血清中IL-10水平明显降低。
7、与健康对照组相比,HSP急性期患儿血清中IL-18水平增高。
8、对于HSP急性期患儿,外周血Th17/Treg比例与血沉水平呈正相关。
9、对于HSP急性期患儿,外周血Th17/Treg比例与患儿临床表现中的受损系统个数呈正相关。
10、对于HSP急性期患儿,外周血Th17/Treg比例与患儿肾损害呈正相关。
11、对于HSP急性期患儿,外周血Th17/Treg比例与抗链球菌溶血素O及补体C3水平无相关性。
结论：1、HSP急性期患儿体内存在Th17细胞、Treg细胞数量异常的情况。相关炎性因子IL-17、IL-10、IL-18浓度也出现异常。Th17细胞、Treg细胞及IL-17、 IL-10、IL-18等炎性因子可能参与了HSP的发病过程。
2、Th17/Treg失衡存在于HSP急性期患儿体内。该失衡与疾病严重程度、肾脏受累等密切相关。Th17/Treg比例也许可以作为衡量HSP急性期患儿发病严重程度及肾脏是否受累以及肾脏受累严重程度的预测指标。
目的：明确HSP急性期患儿体内外周血CD4+T细胞中Tim-3的表达,以及相关检测指标与患儿临床表现和部分实验室检查的相关性,探讨Tim-3在HSP发病过程中的作用临床意义。
方法：选取18名HSP急性期患儿及15名健康对照作为研究对象,流式细胞分析术检测各组研究对象外周血CD4+T细胞中Tim-3的表达。分析HSP急性期患儿CD4+T细胞中Tim-3差异表达的临床意义,并结合相关临床表现及实验室检查,分析其差异表达与HSP急性期患儿的发病及临床表现的关系。
结果：1、与健康对照组相比,HSP急性期患儿外周血CD4+Tim-3+T细胞比例下降。
2、对于HSP急性期患儿,外周血CD4+Tim-3+T细胞比例与血沉水平呈负相关。
3、对于HSP急性期患儿,外周血CD4+Tim-3+T细胞比例与皮疹持续天数、肾损害、ASO、补体C3水平及患儿受损系统的个数无相关性。
结论：1、HSP急性期患儿外周血CD4+T细胞中Tim-3表达异常,且与某些临床指标相关。
2、Tim-3通路有可能参与HSP发病,该指标也许可以作为衡量HSP疾病诊断及病情活动的参考指标。
目的：明确Tim-3在HSP急性期患儿外周血Th17细胞中的表达变化。观察Tim-3通路阻断后HSP急性期患儿外周血单个核细胞分泌IL-17水平的变化。
方法：选取15名HSP急性期患儿及10名健康对照作为研究对象,流式细胞分析术检测各组研究对象外周血Th17+Tim-3+T细胞的表达。抗Tim-3单克隆抗体处理后,酶联免疫吸附法检测HSP急性期患儿外周血单个核细胞表达IL-17水平变化。分析HSP急性期患儿外周血.Th17细胞Tim-3差异表达与疾病的相关性,明确Tim-3/Th17/Treg关联轴在HSP发病机制中的作用。
结果：1、健康对照组Th17细胞表达少量的Tim-3,HSP急性期患儿外周血Th17细胞Tim-3基本无表达,
2、与同型对照相比,Tim-3通路阻断后HSP急性期患儿外周血单个核细胞表达的IL-17虽然升高,但P>0.05,差异无统计学意义。
3、与同型对照相比,Tim-3通路阻断后健康对照组外周血单个核细胞表达的IL-17升高,P<0.05,差异有统计学意义。
4、Tim-3通路阻断后,HSP急性期患儿外周血单个核细胞表达的IL-17高于健康对照组。结论：1、HSP急性期患儿外周血Th17细胞上Tim-3表达异常,Tim-3的异常表达很可能是导致Thl7细胞参与HSP发病机制中的主要原因之一。
2、在HSP急性发病期,Tim-3通路对Th17细胞的调节作用很可能缺失,欲通过Tim-3通路调节Th17细胞在HSP急性发病中的表达及功能,需要考虑更多的因素,寻求更多的途径。
Backgroud
Henoch-Scholein purpura (HSP) is the most common autoimmune small vessel vasculitis disease for children and adolescents. The pathogen and pathogenesis still remain unclear. The people who are in the situation where their risk of HSP is high are the children and adolesecents among the year of5-15. Adults and infants are not susceptible of HSP. One of the main characterics of this disease is non-thrombocytopenic purpura. The joints, gastrointestinal tract, kidney, brain, lungs may be involved, and scrotum could also be involved.The induced reason of this disease may be infection, vaccination, drug and food. Although HSP is considered to be benigh and selfconfinement, it could affect many organs. Then the disease would delay for a long time before it was cured. The anaphylactic purpura nephritis perhaps caused the patients to take medicine constantly. Some patients perhaps had the kidney failure which would affect the treatment and the patients'living qualities. The replase appeared in one third of the patients. One of the reasons which affect the treatment and the protracted course of this disease is the kidney lesion. So it is impotant to undersdand the pathogenesis, seek a good treatment to cure HSP and enhance the patients'living qualities for the clinical pediatrics doctors. In recent years, some researchers utilize the advanced biology techniques to analyze and explore the pathogenisis of HSP from the molecule and gene lay. Combining amount of epidemiological data, they also want to find the effective cure methods. Although they acquired some achievements, there are still many questions about the pathogenisis and diagnosis to be explicit. It is significant to the diagnosis and prognosis of HSP.
Nowadays, some researches have reported the immune dysfunctions of the body were relative to the pathogenesis. Disharmony of T cells, humoral immunologic derangement, diacrisis of the cytokines, abnormal inflammatory response, unusual curor and fibrinolysis pathogenesis and gene susceptibility may be all involved in HSP onset. The basic pathological features are polymorphonuclear cells, lymphocyte cells and eosinophil cells infiltrated aroud the small vessels. IgA compounds, alexin and other immunological compounds deposited on the wall of the small vessels are also the chareactrics of HSP. The serum levels of IgA and some nonspecific proinfiammatory factors such as tumor necrosis factor-a (TNF), interleukin-6(IL-6) raised in the acute HSP acute patients. The above foundings implied inflammation, immunologic derangement and abnormal immune tolerance played an important role for the HSP onset. Sugiyama et al. reported one case of anaphylactic purpura nephritis who was cured by cutting off tonsil and using prednisone. Someya T et al. reported that the patients who are not susceptible for the steroid hormone are remitted effectively by using immunosuppressor. More and more studies indicated that the inflammation spread of HSP could be controlled by immunoregulation.
The acknowledeged typical immunologic derangement feature is the antibodies which were produced by B cells clonal activation aggravated the inflammatory response of HSP. But T cells dysfunction and the relative cytokines ratio imbalance were paid more attention by researchers. Some researches have reported that CD4+T cells ratio imbalance and dysfunction may be the important resons for the abnormal immune tolerance of HSP.
Thl7cells are the new Th subset which is different with Thl and Th2recently and it is defined expressing-IL-17CD4+T cells. TGF-β and IL-6is the necessary cytokines for the Thl7cells differentiation. IL-23is very important for the amplification and maintain of Th17. Th17cells have played an important role for the onset, development and outcome of the autoimmune disease and chronic inflammation. Nowadays, it has found that the levels of IL-17in serum and tissue enhanced in many autoimmune diseases such as rheumatoid arthritis, multiple sclerosis, sysmetic lupus erythematosus and asthma. Meanwhile, the mice of IL-17deficiency or dealing with the IL-17receptor antagonist resisted the adjuvant induced arthritis and experimental autoimmune celebrospinal meningitis. The above results indicated that IL-17may be involved in the onset of autoimmune disease of human and animal. Many researchers began to focus on the relationship between Th17cells and the pathogenesis of HSP. Many studies found there are Th17cells activation phenomenons in the acute HSP children, and this maybe implied Th17cells involved in the pathogenesis. Li YY el al. reported compared with the healthy control, the frequency of Th17cells and Th2cells in the peripheral blood were higher in acute HSP children. Then they indicated Th17cells were relative with HSP onset closely. Jen HY et al. also studied the similar contents and their results showed that the frequency of Th17cells in peripheral blood elevated and the serum levels of IL-17rised significantly. Then they suggensted Th17cells perhaps take part in the inflammatory responses of HSP. Jun Y el al. found that the expressions of ROR-γt which is the special transcription factor of Th17cells were higher in acute HSP acute patients than in healthy control and their results implied Th17cells existed overactivation phenomenons in acute HSP acute patients.11.-18is a new proinflammatory cytokine which could amply the secretion of IL-6and IL-8,while IL-6and IL-8had the significant correlation with the secretion of IL-17, the differentiation ofTh17cells and the onset of HSP.
In the organism, there are many cells which could inhibit and regulate the inflammatory and immune reaction such as dendritic cells,B cells and C4+CD25+regulatory T cells. The regulatory roles of Treg cells are significant. Treg cells play the important roles for the immune tolerance of the organism' self-antigenic and the resistance of immune reactions. Foxp3gene is not only its special sign, but also is important for the activation and regulatory function of Treg cells. Some reports showed that mice model of deficiency of Foxp3gene could suffer the fatal inflammatory reaction which could be inhibited by transferring Treg cells to the mice model. The mechanism of Treg cells to regulate the immune response belonged amount of types, for example Treg cells could accumulate amonge the DCs to inhibit the activation and propagating of the effector T cells. During the inflammatory and immune response, Treg cells could gather the lesion tissue to play its function. Some Chinese researchers found the abnormal quantity and dysfunction of Treg cells in HSP acute patients recently. Qiang W et al. reported that the frequency of Treg cells in peripheral blood decreased in acute HSP acute patients. Jun Y et al. also found the similar research results. They found that the frequency of Treg cells was significantly lower in acute HSP acute patients than in healthy control. Li YY et al. found the different results which revealed the frequency of Treg cells in perapheral blood had no significant difference between the acute HSP acute patients and the healthy control.
In conclusion, although the origin of Treg cells and Thl7cells is CD4+T cells, the imbalance of Thl7/Treg existed in HSP acute patients. The imbalance of Th17/Treg may be related to the HSP onset, the disease severity. It could be the detection index for the HSP severity. It has a great significance to confirm the above opinion for probing the pathogenesis and seeking the effective treatment.
Tim-3is newly molecule which could regulate T cells. Through combining with Galectin-9, it could downregulate Thl cells and Th17cells reaction and play the important role in inflammatory and immune response. The mRNA and protein of Tim-3, Galectin-9, T-bet were abnormal in autoimmune diseases patients and animal models such as non-obese diabetes and experimental autoimmune celebrospinal meningitis which all belonged to Thl type diseases. The expression of Tim-3in CD4+T cells became the research hot spot recently. Jones et al. reported the expression of Tim-3in peripheral blood rised in human immunodeficiency virus infectious patients. Ying Liu et al. found the expression of Tim-3mRNA rised in acute rheumatoid arthritis patients. Activating the access of Tim-3/Galectin-9to down-regulate Th17cells had been paid more attention by some researchers.
Nowadays, researchers began to keep a watch to the relationship between Tim-3/Th17/Treg and HSP.It has been found that using cytokines or receptor antagonism protein could benefit the gene therapeutic. But the function and the therapeutic effect of the singal cytokine are limited. Focusing on the upstream cytokines and proteins which involved in the pathogenesis became the new research tendacy.
In this study, Th17cells, Treg cells, Tim-3and other relative cytokines had been detected in different groups. The aim of this research is to discuss the role of Th17/Treg and Tim-3in the pathogenesis. The results maybe could benefit to making clear the pathenesis of immune tolerance and maintain, expounding the cytokines confusion phenomenon. The results maybe also could provide the new thesis and tactics for the HSP treatment.
Objective: The aim of this study is to identify the expression features of Thl7/Treg in peripheral blood in HSP acute patients and the relativity among the expression features of Th17/Treg, clinical manifestations and some laboratory inspections. Another aim of this study is to probe the role and cinical signifieience of Th17/Treg in the pathogenesis of HSP.
Methods:23acute HSP acute patients and18healthy controls took part in this study. The frequencies of Thl7and Treg in peripheral blood were detected by How cytometry. The serum levels of IL-17, IL-10and IL-18were examined by enzyme linked immunosorbent assay. The changes of Th17/Treg ratio were analyzed. The relationships among the imbalance of Th l7/Treg, the onset and clinical manifestation were also analyzed.
Results:1、The frequency of Th17cells in peripheral blood was higher in HSP acute patients than in healthy controls.
2、The frequency of CD3+CD8-IL-21+T cells in peripheral blood was higher in HSP acute patients than in healthy controls.
3、The frequency of Treg cells in peripheral blood was lower in HSP acute patients than in healthy controls.
4、The ratio of Th17/Treg in peripheral blood was higher in HSP acute patients than in healthy controls.
5、The serum levels of IL-17were higher significantly in HSP acute patients than in healthy controls.
6、The serum levels of IL-10were lower significantly in acute HSP acute patients than in healthy controls.
7、The serum levels of IL-18were higher in acute HSP acute patients than in healthy controls.
8、The ratio of Th17/Treg is positive related to the erythrocyte sedimentation rate for acute HSP acute patients.
9、The ratio of Th17/Treg is positive related to the numbers of lesion systems for acute HSP acute patients.
10、The ratio of Th17/Treg is positive related to the kidney lesions for HSP acute patients.
11、The ratio of Th17/Treg has no correlation with the levels of anti-streptolysin O (ASO) and completment3(C3).
Conclusions:1、The frequencies of Th17and Treg in peripheral blood were abnormal in acute HSP acute patients. The concentrations of IL-17and IL-10were also unusual in serum in acute HSP acute patients. Thl7cells、Treg cells、IL-17、IL-10and IL-18maybe involve in the pathogenesis.
2、The imbalance of Thl7/Treg existed in acute HSP patients. The imbalance of Th17/Treg had significant correlation with the disease severity and kidney lesions. The ratio of Th17/Treg maybe could become the forecast index to measure the HSP severity and kidney lesions.
Objective: The aim of this study is to identify the expression of Tim-3in CD4+T cells in MSP acute patients. The correlations among the detected indexes, the clinical manifestation and laboratory inspections were analyzed. The end aim of this part research is to probe the role and clinical significance of Tim-3in the pathogenesis.
Methods:18HSP acute patients and15health cases took part in this research. The frequencies of CD4+Tim-3+T cells in peripheral blood were detected by Flow cytometry. The expressions of CD4+Tim-3+Tcells were analyzed. The relationships among the detected indexes, the onset and clinical manifestation were also analyzed.
Results:1、The frequencies of CE4+Tim-3+Tcells were lower in acute HSP patients than in healthy controls.
2、 The frequencies of CD4+Tim-3+T cells were negative related with ESR in HSP acute patients
3、The frequencies of CD4+Tim-3+Tcells had no correlation with rash duration in days, kidney lesions. ASO. C'3and the numbers with lesion systems in acute HSP patients.
Conclusions:1、The expression of Tim-3in CD4+T cells in acute HSP acute patients were abnormal. They had correlatDion with the disease severity and some clinical indexes.
2、The passage of Tim-3maybe involve the onset of HSP. It perhaps could become the reference index to measuer HSP activity and severity.
Objective:The aim of this study is to identify the expression of Thl7+Tim-3+T cells in the peripheral blood in acute HSP patients and to observe the expression of IL-17in peripheral blood mononuclear cells by blocking the road of Tim-3.
Methods:15acute patients and10health children took part in this research. The frequencies of Thl7+Tim-3+Tcells in peripheral blood were detected by Flow cytometry. The levels of IL-17cells were detected by enzyme linked immunosorbent assay when the peripheral blood mononuclear cells were dealed with Tim-3monoclonal antibody. The relationships among the detected indexes, the onset and clinical manifestation were also analyzed to identify the role of Tim-3/Thl7/Treg in the pathogenesis.
Results:1、The frequencies of Thl7+Tim-3+Tcells were low in healthy controls. It had no expression of Tim-3on Th17cells in the peripheral blood in acute HSP patients.
2、Compared with the homotype contrast, the secretion levels of IL-17of the peripheral blood mononuclear cells did not rise by the blocked Tim-3passage in the acute HSP patients.
3、Compared with the homotype contrast, the secretion levels of IL-17of the peripheral blood mononuclear cells rised in healthy controls.
4、After the Tim-3passage was blocked, the secretion of IL-17of the peripheral blood mononuclear cells in acute HSP patients was higher than it in healthy controls.
Conclusions:
1、The expression of Tim-3in Th17cells in peripheral blood mononuclear cells in acute HSP acute patients were abnormal. This may be one of the main reasons which leaded Th17cells to be involved in the pathogenisis of HSP.
2、During the HSP acute onset, the adjusting roles of Tim-3passsage for Th17cells probably were deficent. If we want to adjust the numbers and function of Th17cells through Tim-3passage in HSP acute onset, we should explore more motheds and consider more causes.
引文
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