不明原因习惯性流产患者Th1/Th2型细胞因子的检测

目的 :了解不明原因习惯性流产 (UHA)患者对滋养细胞抗原刺激产生Th1、Th2型细胞因子的水平 ,探讨其在UHA发病中的作用。方法 :选取 5 4例UHA患者 ,35例为未妊娠者 ,为UHA未孕组 ,19例为有UHA病史 ,现在确定妊娠并难免流产者 ,为UHA难免流产组。分别选取 15例正常未孕妇女及正常妊娠者作为对照组。应用酶联免疫吸附法检测未孕各组经滋养细胞抗原刺激的外周血单个核细胞 (PBMC)及妊娠各组PBMC与蜕膜单个核细胞 (DMC)培养上清液中IL 2、IFN γ、IL 4、IL 10的水平。结果 :①在最佳诱导时间下 ,UHA未孕组PBMC产生IL 2、IFN γ的水平明显高于正常未孕组 (P均 <0 0 5 ) ,而IL 4、IL 10水平明显低于正常未孕组 (P均 <0 0 5 )。②UHA难免流产组PBMC及DMC产生的IL 2、IFN γ水平均明显高于正常妊娠组 (P均 <0 0 5 ) ,而IL 4、IL 10水平则明显低于正常妊娠组 ,差异均有显著性 (P均 <0 0 5 )。两组PBMC产生的各细胞因子水平均低于同组DMC ,差异有显著性 (P <0 0 5 )。结论 :UHA患者对滋养细胞抗原产生以Th1型反应为主的免疫应答 ,产生大量Th1型细胞因子 ,导致妊娠丢失。     

不明原因习惯性流产患者主动免疫治疗前后TH1/TH2型细胞因子水平的变化

通过检测原因不明习惯性流产 (ｕｎ ｅｘｐｌａｉｎｅｄｈａｂｉｔｕａｌａｂｏｒｔｉｏｎ ,ＵＨＡ)患者外周血单个核细胞 (ＰＢＭＣ)经滋养细胞抗原刺激产生各细胞因子的水平 ,探讨ＴＨ1/ＴＨ2因子在ＵＨＡ发病及主动免疫治疗中的作用。ＵＨＡ患者 35例 ( 2 7.5± 3.3岁 ) ,均接受 2疗程小剂量主动免疫治疗 ,免疫原采用丈夫或健康无关第三个体淋巴细胞 ,免疫剂量为 2× 10 7～ 3× 10 7个淋巴细胞 ,间隔 3周 ,共免疫 4次 ,在治疗前及免疫结束后 3周分别抽取外周血。同时选取 15名育龄健康未孕妇女 (至少有1次足月活产史 )作为正常对照组。…     

原因不明习惯性流产者免疫治疗前后APCA的比较

目的寻求治疗原因不明习惯性流产新的有效途径,探讨抗父体淋巴细胞毒抗体主动免疫治疗前后的变化.方法采用丈夫淋巴细胞对32例原因不明习惯性流产患者在怀孕前后各给予两次免疫治疗,20例同期在本院就诊,年龄组相当,有过足月分娩史的妇女作为对照组.对20例对照组及32例流产组治疗前后,分别检测抗父体淋巴细胞毒抗体.结果治疗组妊娠成功率为84.4%,对照组妊娠成功率为25%.两组比差异显著(P＜0.01=).对照组APCA阳性率为80%,流产组在治疗前的APCA为9.4%,两组比差异显著(P＜0.01=);流产组治疗后的APCA为78%,治疗前与治疗后比差异显著(P＜0.01=).结论主动免疫治疗可以提高习惯性流产患者妊娠成功率,也可诱导母体产生保护性抗体.     

原因不明习惯性流产免疫治疗前后血清TGF-β1变化研究

目的检测原因不明习惯性流产(UHA)患者免疫治疗前后血清中TGF-β1变化,探讨其在UHA发病及治疗中的作用。方法采用皮下注射丈夫淋巴细胞的方法治疗UHA患者;应用ELISA法检测正常非孕妇女30例和UHA妇女30例免疫治疗前后血清TGF-β1含量(Pg/mL)。结果UHA患者血清中TGF-β1含量(10178.50±3258.60)明显低于正常非孕妇女(11988.10±3423.65),P<0.025=;24例妊娠成功者治疗后血清中TGF-β1含量(12801.21±3510.97),与治疗前相比明显升高,(P<0.025=;6例妊娠失败者治疗后血清中TGF-β1含量(11079.50±3227.21),与治疗前比较无明显变化,(P>0.05)。结论血清中TGF-β1水平降低可能与UHA的发生有关,免疫治疗可上调血清中TGF-β1水平,诱导母体免疫耐受,使妊娠成功。     

高迁移率族蛋白B1与原因不明复发性流产患者Th1/Th2平衡的相关性

目的 探讨HMGB1和Th1/Th2型细胞因子在原因不明复发性流产（URSA）患者外周血中的表达及相关性研究。方法 纳入2019年6月至2020年6月期间在深圳市妇幼保健院妇科就诊的100例URSA患者为URSA组,分别于免疫治疗前、后采集患者外周血。以同期100例体检健康妇女为对照组。比较两组外周血中Th1、Th2细胞比例、Th1/Th2比值、IL-2、IFN-γ、IL-4和IL-10和HMGB1的表达。比较治疗后不同妊娠结局URSA患者细胞因子和HMGB1表达水平。采用Pearson相关分析法分析细胞因子和HMGB1的相关性。结果 URSA治疗前与治疗后和对照组相比、妊娠成功组与失败组相比,IL-2、IFN-γ和HMGB1均升高,IL-4和IL-10均降低（P<0.05）;URSA治疗前与对照组比,Th1细胞比例、Th1/Th2值升高,Th2细胞比例降低（P<0.05）。HMGB1与IL-2和IFN-γ呈正相关,与IL-4和IL-10呈负相关（均P<0.01）。结论 URSA的发病与Th1/Th2细胞平衡向Th1方向偏移有关,HMGB1可能参与了Th1/Th2失衡...     

主动免疫治疗原因不明习惯性流产致荨麻疹反应一例

主动免疫治疗原因不明习惯性流产方法简单,治疗成功率高,对孕妇的副作用少见报道。在实际工作中发现免疫治疗后致妻子荨麻疹反应一例,报道如下。临床资料患者陈某,31岁,汉族,发生早期流产4次。排除因遗传、内分泌、解剖异常、感染、自身免疫病等常见原因引起的流产,诊断为原因不明习惯性流产。丈夫身体健康无传染病。采用免疫疗法对妻子进行主动免疫治疗。具体方法见文献[1]。治疗6h后,在妻子的手背、膝盖、腋窝、腹股沟等处出现对称性红斑,瘙痒,无发热、寒战。经静脉注射葡萄糖酸钙,口服息斯敏,1h后症状逐渐消失,诊断为荨麻疹反应。在过后…     

绒毛和蜕膜中的Th1,Th2细胞因子水平与反复流产的关系

目的　了解Th1,Th2细胞因子在反复流产患者绒毛和蜕膜中的浓度以及与反复流产的关系。方法　采用放射免疫的方法 (RIA)对 80例反复流产患者和 2 8例正常妇女的绒毛和蜕膜中Th1,Th2细胞因子进行检测。结果　反复流产患者中绒毛、蜕膜Th1,Th2细胞因子的浓度增高 ,与正常对照组相比 (P <0 0 5 ,0 0 1) ;Th1/Th2偏移。结论　Th1、Th2型细胞因子的异常分布与妊娠丢失有关     

新生儿巨细胞病毒肺炎Th1/Th2细胞因子测定及意义

目的探讨新生儿巨细胞病毒肺炎血清细胞因子IL4、IFN-7、TNF—α水平及意义。方法选取25例确诊为新生儿巨细胞病毒肺炎．并将其分为丙种球蛋白治疗组和更昔洛韦治疗组，应用ELISA法检测治疗前和疗程结束后血清细胞因子IL-4、IFN-γ、TNF-α的浓度，另选取本院产科同期出生的足月正常新生儿15例为正常对照组，用相同的方法检测其血清中细胞因子IL-4、IFN-γ、TNF-α的浓度。结果相对于健康新生儿．CMV—IgM阳性患儿血清IFN-γ及TNF—α水平升高．差异有统计学意义（t值分别为2．65及3．16．P〈0．05）；而IL-4水平降低，差异有统计学意义（t=2．49．P〈0．05）。丙种球蛋白治疗组（IVIG）和更昔洛韦治疗组治疗前IFN-γ、IL-4、TNF—α水平比较，差异无显著性（t值分别为1．85、1．71及1．76．P〈0．05）；IVIG治疗组中．治疗前后比较．IFN-γ及TNF—α水平降低，差异有统计学意义（t值分别为3．98及5．16，P〈0．01）；而IL-4水平升高，差异有统计学意义（t=2．55，P〈0．05）。更昔洛韦治疗组中．治疗前后比较，IFN-γ及TNF—α水平变化不明显．差异无统计学意义（t值分别为1．75及1．16．P〉0．05）；而IL-4水平无明显降低．差异无统计学意义（t=1．89，P〉0．05）。结论巨细胞病毒肺炎新生儿Th1／Th2存在平衡失调，代表Thl细胞功能水平的细胞因子IFN-γ水平明显增高，呈现低水平的Th1相对优势，表明感染后．免疫平衡遭到破坏．细胞因子分泌失衡，造成机体的免疫炎症损伤，IVIG治疗可以纠正这-平衡失调，提示在新生儿巨细胞病毒肺炎除单-抗病原治疗外，应重视免疫调节治疗。     

主动免疫疗法治疗习惯性流产的临床研究

目的探讨主动免疫治疗习惯性流产患者的效果。方法无菌采取丈夫的静脉血20ml,分离淋巴细胞后于孕前,孕后皮内注射于妻子前臂内侧,使其产生主动免疫。结果治疗组：经主动免疫治疗后36例妊娠,其中分娩25例,中晚期妊娠5例,流产6例,妊娠成功率83.3%（30/36）对照组：未经主动免疫治疗21人,其中分娩5例,正在妊娠3例流产13例,妊娠成功率38%（8/21）,两组相比,有显著差异性（P〈0.05）结论主动免疫治疗习惯性流产疗效肯定,治疗后妊娠成功率高。     

白三烯受体拮抗剂对呼吸道合胞病毒肺炎血清Th1/Th2细胞因子水平影响的研究

目的探讨白三烯受体拮抗剂对呼吸道合胞病毒肺炎患儿血清中Th1／Th2细胞因子、半胱氨酰白三烯水平的影响，研究降低呼吸道合胞病毒肺炎发展为哮喘的有效干预途径。方法将37例呼吸道合胞病毒肺炎患儿分为白三烯受体拮抗剂干预组：顺尔宁，4mg qd，疗程12周，糖皮质激素吸入干预组：出院后给予糖皮质激素吸入，200μg qd／bid，疗程12周。两组患儿入院后24h内及疗程结束用酶联免疫法检测CysLTs、IFN-γ、IL-4。另选10例健康同龄儿童血清标本作对照。结果呼吸道合胞病毒肺炎患儿血清中Th1／Th2细胞因子表达存在失衡，血清CysLTs水平明显高于健康对照组（t=7．85，P〈0．05）；顺尔宁干预组和糖皮质激素吸入干预组均能纠正Th1／Th2细胞因子失衡，差异无统计学意义（P〉0．05）。糖皮质激素吸入干预组血清CysLTs水平治疗前后无明显变化，差异无统计学意义（P〉0．05），顺尔宁干预组血清Cys仉水平治疗后明显下降，差异有统计学意义（P〈0．05）。结论呼吸道合胞病毒肺炎患儿存在Th1／Th2细胞因子失衡、血清CysLTs水平较健康同龄儿童明显升高，与哮喘有相似之处。白三烯受体拮抗剂早期干预能纠正Th1／Th2细胞因子失衡，降低血清CysLTs水平。     

Changes in Regulation of Oxidase Activity of Peripheral Blood Granulocytes in Women with Habitual Abortions

Generation of active oxygen forms by blood granulocytes was studied in women with a history of habitual abortions (2-3 spontaneous abortions in the first trimester, undeveloped pregnancies). The level of spontaneous luminol-dependent chemiluminescence of nonfractionated peripheral blood was increased in this patient population (study group) in comparison with women with normal reproductive function (reference group). The two groups differed by the level of activation of respiratory burst induced by opsonized zymosan and by activity of isolated granulocytes in response to chemotactic peptide N-formyl-methionyl-leucyl-phenylalanine (1-50 microM). Differences in the effects of inhibitor of tyrosine protein kinases and protein phosphatases and inhibitor of mitogen-activated proteinkinase p38 MAPK were detected. The results attest to predisposition to oxidative stress and poor cytotoxic functions of granulocytes in women with habitual abortions, which can be due to specific features of regulation of oxidase activity by tyrosine protein kinases and protein phosphatases and by p38 MAPK.     

Influence of Immunotherapy on Antisperm Antibody Titer in Unexplained Recurrent Aborters

PROBLEM: The mechanism of the beneficial effect of immunotherapy for human reproductive wastage remains to be elucidated. Because some women with unexplained recurrent spontaneous abortion are immunized with their partner's lymphocytes, it is important to determine whether such immunization results in elevation or enhancement of immunity to spermatozoa, because antigenic cross-reactivity between lymphocytes and spermatozoa has been reported. METHOD: The present study was initiated to evaluate the changes in antisperm antibody titer and lymphocyte subsets after immunotherapy as compared to before immunotherapy. Antisperm antibody detection was performed by SpermCheck Assay, which is based on a modification of the immunobead test. Maternal lymphocyte subsets were analyzed in two-color flow-cytometric experiments. RESULTS: The percentage of antibody-positive sperm decreased significantly (P = 0.0008) after immunotherapy. The percentage of B(CD19 +) cells (P = 0.0003), cytotoxic T(CD8 + and CD11 b -) cells (P = 0.02) and the Th/Ts ratio (P = 0.005) decreased significantly, while suppressor T(CD8 + and CD 11b +) cells increased significantly (P = 0.0002) after the immunotherapy. This suggests that cell-mediated immunosuppression was induced by immunotherapy. CONCLUSION: The data of the present study suggest that antisperm antibodies have potential for use as a marker for a deficiency in maternal genital tract immunosupressor mechanisms and that immunotherapy could be an effective treatment for women with antisperm antibodies who have unexplained recurrent abortions.     

Intravenous immunoglobulin treatment in women with recurrent abortions: increased cytokine levels and reduced Th1/Th2 lymphocyte ratio in peripheral blood

PROBLEM: The aim of this study was to investigate changes in peripheral blood Th1/Th2 cytokine levels and lymphocyte ratios after massive intravenous immunoglobulin (MIVIg) treatment for women with recurrent spontaneous abortion (RSA) of unexplained etiology. METHOD OF STUDY: Serum Th1 (IFN-gamma, TNF-alpha) and Th2 cytokine (IL-4, IL-10) levels were assessed by ELISA methods (n = 9) and peripheral blood Th1/Th2 lymphocyte ratios (n = 4) by flow cytometry before and after MIVIg treatments in women with four or more consecutive RSA. RESULTS: Pre-treatment serum IFN-gamma (0.06 +/- 0.09 pg/mL, mean +/- SD), TNF-alpha (0.21 +/- 0.45 pg/mL), IL-4 (0.70 +/- 1.16 pg/mL), and IL-10 (1.12 +/- 1.67 pg/mL) increased to 0.17 +/- 0.16 pg/mL, 0.77 +/- 0.28 pg/mL, 1.82 +/- 0.89 pg/mL, and 3.44 +/- 0.48 pg/mL, respectively, after MIVIg treatments (P < 0.05). CD4-positive IFN-gamma/IL-4 lymphocyte ratios (17.3 +/- 9.1) were reduced to 11.5 +/- 7.1 after treatment (P < 0.05). CONCLUSIONS: Massive intravenous immunoglobulin treatments increased peripheral blood cytokine levels and decreased Th1/Th2 lymphocyte ratios; thus, MIVIg treatments modify the peripheral Th1/Th2 balance.     

Balance of Th1/Th2 Cytokines Associated with the Preventive Effect of Incomplete Freund's Adjuvant on the Development of Adjuvant Arthritis in LEW Rats

Complete Freund's adjuvant (CFA) could induce adjuvant arthritis (AA) in LEW rats and incomplete Freund's adjuvant (IFA) could induce oil induced arthritis (OIA) in DA but not in LEW rats. Lymph node cells (LNCs) from these AA and OIA rats showed increased mRNA expression of IFN-gamma, IL-2 and TNF-alpha but not IL-4. LNCs from IFA immunized LEW rats showed increased expression of IL-4, reduced expression of IFN-gamma and TNF-alpha and no IL-2, in contrast to IFA immunized DA rats. The pretreatment of IFA before CFA challenge could completely prevent AA in LEW rats and their LNCs showed increased expression of IL-4 and IFN-gamma but not IL-2 and TNF-alpha. In F1 (LEW x DA) rats, IFA could not induce OIA but the pretreatment of IFA before CFA challenge could induce very mild AA with 80% incidence, LNCs showing an elevated expression of all the above cytokines. These findings suggest that increased Th1 cytokine expression is associated with disease development and that increased IL-4 expression or the balance of Th2 over Th1 cytokine expression plays an important regulatory role in disease development.     

类风湿关节炎患者关节中Th1/Th2型细胞因子的模式及临床意义

目的　分析类风湿关节炎 (RA)患者滑膜液及外周血中Th1/Th2型细胞因子网络的偏移及其在疾病过程中的意义。方法　用酶联免疫斑点法 (enzymelinkedimmunospotassay ,ELISPOT) ,检测RA患者滑膜液单个核细胞 (SFMC)和外周血单个核细胞 (PBMC)中的Th1和Th2细胞 ,并分析Th1/Th2细胞的比值与血沉 (ESR)和C 反应蛋白 (CRP)的相关性。结果　与PBMC相比较 ,RA患者SFMC中CD3 T细胞的百分率 ,Th1细胞及Th1/Th2细胞的比值显著升高P <0 0 1) ,且此比值与患者的ESR和CRP均呈正相关(分别为r =0 84,P <0 0 1和r =0 74,P <0 0 2 )。结论　在RA患者关节中Th1细胞明显增多并占优势 ,Th1/Th2细胞的比值与疾病的活动程度明显相关 ,Th1/Th2细胞的平衡在RA的发病机制及疾病进展中可能具有重要的作用     

Th1、Th2、Th17型细胞因子与糖尿病肾病相关性的研究

糖尿病肾病(diabetic Nephropathy,DN)是导致终末期肾脏病(end-stage renal disease,ESRD)的最主要病因,因此,早期诊断和治疗是糖尿病肾病的诊治要点。但目前糖尿病肾病的确切发病机制尚未完全明确,糖尿病肾病的发生发展与血流动力学改变和代谢的紊乱、氧化应激和炎症等多种因素有关,而细胞因子在2型糖尿病及其相关肾脏并发症的病因、发病机制中也起着重要的作用,各种细胞因子的识别将为糖尿病肾病的诊治提供新的潜在治疗靶点。文章就Th1、Th2、Th17型细胞因子与DN相关性的研究作了综述。     

CpG ODN对rHBsAg免疫小鼠Th1/Th2型免疫应答的影响

目的：初步探讨CpC寡脱氧核苷酸(CpG ODN)与重组乙型肝炎表面抗原(rHBsAg)联合免疫小鼠的Th1／Th2型免疫应答效应。方法：BALB／c小鼠经后腿胫骨前肌免疫2次，ELISA法检测血清乙型肝炎表面抗体(抗-HBs)IgG亚类IgG2a/IgG1的比值；生物活性法检测脾细胞诱生上清中的IFN-γ和IL-2含量；ABC-ELISA法检测小鼠血清中IL-4、IL-10及IL-12含量。结果：加CpG ODN组与单独注射rHBsAg组相比：抗-HBs IgG亚类IgG2a／IgG1比值明显高；Th1型细胞因子IFN-γ和IL-2的表达增强，抑制Th2型细胞因子IL-4和IL-10的产生。结论：CpCODN能够明显增强rHBsAg免疫小鼠Th1型抗体亚类IgG2a的产生，并且诱导Th1型细胞因子的表达，抑制Th2型细胞因子的表达。     

Histamine H1-receptor antagonists with immunomodulating activities: potential use for modulating T helper type 1 (Th1)/Th2 cytokine imbalance and inflammatory responses in allergic diseases

Being a first-line treatment for hypersensitivity allergic disease, histamine H1-receptor antagonists possess anti-inflammatory activity in addition to being H1-receptor antagonists. While it is not purely a histamine-related condition, hypersensitivity allergic disease is associated with an increase in the number of T helper type 2 (Th2) cells and Th2 cytokines, and a decrease in the number of Th1 cells and Th1 cytokines. Suppression of Th2-type cytokine production in addition to H1-receptor blockade may therefore represent a successful therapeutic strategy for the treatment of hypersensitivity allergic diseases. H1-receptor antagonists have been reported to modulate immune cascade at various points by acting on T cell-related inflammatory molecules, including adhesion molecules, chemokines and inflammatory cytokines. These effects of H1-receptor antagonists may be optimized for the treatment of allergic diseases. Besides their ability to regulate inflammatory molecules, some H1-receptor antagonists have been reported to down-regulate Th2 cytokine production. In particular, it has been shown that several H1-receptor antagonists specifically inhibit the production of Th2, but not Th1, cytokines. Accumulating evidence indicates a crucial role for Th1/Th2 cytokine imbalance on the development of allergic diseases. Accordingly, the use of H1-receptor antagonist with Th2 cytokine inhibitory activity to modulate Th1/Th2 cytokine imbalance might be a favourable strategy for the treatment of hypersensitivity allergic diseases. Furthermore, the identification of H1-receptor antagonists which possess immunoregulatory activities in addition to their anti-histamine activity will provide an important insight into the development of novel immunoregulatory drugs.