口腔白斑HLA-DR表达与中药治疗的对比研究

【目的】探讨口腔白斑 (OLP)的发病机制及中药Ⅰ号口服液的作用机制。【方法】采用SP法检测12 0例OLP治疗前后病损区角朊细胞 (KC)异常表达人白细胞分化抗原DR区 (HLA DR)抗原的情况。【结果】12 0例OLP标本的黏膜上皮细胞均不同程度的表达HLA DR的阳性KC ,其数量及表达程度与中药Ⅰ号口服液的疗效呈负相关 ,不同疗效组间差异有显著性 (P <0 .0 1)。【结论】本结果提示 ,OLP的发病机制可能是机体免疫功能低下引起的自身免疫反应。推测中药Ⅰ号口服液的作用机制是调整机体的免疫功能 ,抑制自身免疫反应 ,从而取得较好的临床疗效。     

血必净对多脏器功能障碍综合征单核细胞HLA-DR表达影响的研究

目的 :观察多脏器功能障碍综合征 (MODS)患者早期发病的免疫功能状态及应用中西医结合治疗的效果。方法 :采用免疫荧光技术连续监测 2 8例 ICU病房中严重创伤和感染致 MODS患者的外周血单核细胞表面人类白细胞抗原 DR位点 (HL A DR)抗原的表达 ,以及采用中药血必净治疗后对其产生的影响。结果 :发生MODS创伤感染患者 HL A DR抗原表达水平比健康人群和未发生 MODS创伤感染患者显著降低 (P<0 .0 5或 P<0 .0 1)。中药血必净治疗组患者比未用中药治疗的对照组患者的 HL A DR表达明显增强。结论 :MODS早期机体产生大量炎性介质并释放 ,而单核细胞 HL A DR抗原表达减少 ,正常免疫功能受到抑制 ;中药血必净有促进免疫功能恢复的作用。     

HLA基因表达调控的研究进展

在器官移植中,人类白细胞抗原(HLA)的相合程度直接影响到移植器官的预后,完全匹配供体的缺乏制约了器官移植的广泛开展。为了降低移植后免疫排斥反应强度,人们试图对移植器官进行基因改造,使主要刺激免疫排斥反应的白细胞抗原低表达或不表达,为此人们在HLA表达调控的基础理论方面进行了大量研究。HLA位于第6号染色体短臂6p21.3区域,跨度约为4MB。在该区域中集中了近180个功能基因,40%与免疫系统功能相关,其中包括HLA Ⅰ／Ⅱ类基因及新近发现的MIC、DMA、DMB等基因群。HLA基因在人群中呈现复杂的多态性,是免疫反应个体差异的分子基础。上述基因尤其是HLA Ⅰ／Ⅱ类基因编码的糖蛋白产物在抗原的加工、处理和递呈等环节中起重要作用。HLA Ⅰ类基因分为经典型A、B、C和非经典型E、G、F两类;HLA Ⅱ类基因区主要有DQ、DR、DP等座位。HLA Ⅰ／Ⅱ类基因的产物可分别将内源性和外源性抗原肽递呈给淋巴细胞,诱导机体产生特异的免疫应答。Ⅰ类分子表达于所有有核细胞表面,Ⅱ类分子则主要表达于激活的T淋巴细胞、B淋巴细胞、巨噬细胞及DC细胞表面。HLA Ⅰ类和Ⅱ类分子在群体和细胞中的特异性表达受到许多顺式和反式作用因子的严格调控,以此来保证其正常免疫学功能的发挥。HLA基因表达调控的研究进展很快,以下是对近来研究进展的简要综述。     

特发性血小板减少性紫癜患者血小板对自身淋巴细胞的异常激活

目的　探讨特发性血小板减少性紫癜(ITP)患者血小板表面人类白细胞抗原 (HLA- DR)的表达和CD4+T淋巴细胞的活化状态。方法　采用流式细胞术检测 60例ITP患者和 60例正常人血小板表面HLA DR的表达水平和自身血小板活化的淋巴细胞产生白细胞介素 2(IL -2)水平。结果　ITP患者血小板表面HLA- DR的表达量为 0 .808%±0 .218%,正常对照组为 0. 025%±0. 019%,两者相比差异具有统计学意义(P<0. 01)。ITP患者CD4+T淋巴细胞经自身血小板激活后,IL 2的表达量为 5 .1% ±1 23%,较正常对照组(0 .0% )有明显差异(P<0 .01)。结论　ITP患者在自身血小板HLA DR抗原的作用下,出现了自身反应性T淋巴细胞的异常活化,T淋巴细胞处于高活性状态。     

昆明山海棠配合中药方剂治疗口腔扁平苔藓92例临床观察

【目的】比较两种方法治疗口腔扁平苔藓（OLP）的临床疗效。【方法】92例OLP病人随机分成治疗组和对照组各46例,治疗组采用昆明山海棠和中药方剂治疗,对照组单用昆明山海棠治疗,治疗两个月,比较两组疗效。【结果】治疗组显效率和总有效率均高于对照组（P〈0.05）。【结论】昆明山海棠配合中药方剂治疗OLP疗效显著。     

大承气汤对危重症患者单核细胞表面人白细胞抗原DR表达的影响

目的 观察大承气汤对严重创伤、感染患者的免疫功能的影响及治疗效果。方法 45例严重创伤、感染患者随机分为2组，治疗组24例应用大承气汤鼻饲治疗，对照组21例采用常规治疗。观察患者外周血单核细胞表面人白细胞抗原DR（HLA－DR）表达变化及多脏器功能障碍综合征（MODS）发生情况。结果 对照组HLA－DR恢复缓慢，治疗组HLA－DR恢复迅速；对照组MODS发生率为66．67％，治疗组MODS发生率为29．17％（P＜0．05）。结论 大承气汤可调节患者的免疫功能，降低严重创伤、感染后MODS发生率。     

HLA－B27阳性与阴性强直性脊柱炎患者多项免疫指标的对比

目的　了解HLA B2 7抗原与强直性脊柱炎 (AS)患者机体免疫功能的关系。方法　T细胞亚群的检测采用桥联酶标法 ;免疫球蛋白、C反应蛋白的检测采用速率散射比浊法 ;白细胞介素 6 (IL 6 )、肿瘤坏死因子α(TNFα)的测定采用双抗体夹心ELISA。结果　HLA B2 7抗原阳性患者各项免疫指标与正常人相比差异均有显著性 ,而HLA B2 7阴性患者各项免疫指标与正常人的差异则较小。结论　HLA B2 7抗原在AS发病过程中可能起了重要作用 ,并对机体的免疫功能产生了一定影响     

动态监测重症监护室患者HLA—DR＋／CDl4＋变化的临床意义

目的在重症监护室（ICU）患者中动态监测外周血中人类白细胞抗原（HLA）-DR＋／CDl4＋、CDl4＋的表达,并评价HLA—DR＋／CDl4＋的临床意义。方法应用流式细胞术,测定入院后第l、3、7、14天ICU患者外周血中HLA—DR＋／CDl4＋、CDl4＋的表达,并进行脓毒症相关性器官衰竭（SOFA）评分。结果入院后动态监测第1天。两组HLA—DR＋／CDl4＋表达差异无统计学意义（t=0．86,P〉0．05）;第3天、第7天和第14天时存活组HLA—DR＋／CDl4＋表达高于死亡组,差异均有统计学意义（t分别=3．34、6．61、7．60,P均〈0．05）;第7天和第14天时存活组CDl4＋表达高于死亡组,差异均有统计学意义（t分别：3．46、2．56,P均〈0．05）;SOFA评分第7天和第14天时低于死亡组,差异均有统计学意义（t分别=2．08、2．53,P均〈0．05）。结论单核细胞活化功能表达持续低下可提示机体处于免疫抑制状态．动态监测HLA—DR＋／CDl4＋是监测患者免疫功能的早期、连续的方法。     

甲状腺功能亢进症患者药物治疗前后外周血树突细胞亚群的变化

甲状腺功能亢进症(简称甲亢)是抑制性T淋巴细胞功能缺陷的一种自身免疫性疾病。树突细胞(dendriticcell,DC)是专职的抗原提呈细胞,DC根据细胞表型常分为2个亚群:DC1表面标志为L in-人白细胞抗原(HLA)DR CD11 c CD123-,主要发挥抗原提呈的功能,促进细胞免疫的发生;DC2表面标志为     

器官移植中人白细胞抗原分型研究的进展

免疫排斥反应对临床器官移植的成功与否有至关重要的影响。组织相容性抗原———人白细胞抗原 (HLA)的不同 ,可引起免疫排斥反应 ,它是导致移植物丧失功能的主要原因之一。器官移植HLA配型的方法现已由传统的血清学、细胞学方法 ,发展到运用聚合酶链式反应 (PCR)技术进行基因配型。临床合理运用这些方法进行供受者的免疫学选配 ,是防止和减轻排斥反应的关键[1]。一、器官移植与HLA分型HLA分为Ⅰ类抗原 (HLA A、B、C )、Ⅱ类抗原 (HLA DR、DP、DQ)和Ⅲ类抗原。大量研究表明HLAⅠ类和Ⅱ类抗原尤其是HLA A、B、DR、DQ ,在移植…     

Expression of HLA-DR molecules by keratinocytes, and presence of Langerhans cells in the dermal infiltrate of active psoriatic plaques

Immunoperoxidase staining of skin sections and immunofluorescence analysis of keratinocyte suspensions obtained from suction blisters of psoriatic plaques were performed using an mAb, Josh 524.4.1, and Fab'2 fragments of a rabbit antiserum, both of which are directed against nonpolymorphic determinants of HLA-DR molecules. HLA-DR+ keratinocytes were present in plaques, but not normal-appearing skin, from a significant portion of patients with active psoriasis. Double-labelling immunofluorescence experiments with either the monoclonal or polyclonal anti-HLA-DR antibody, in conjunction with the mAb OKT6, which identifies DR+ Langerhans cells, demonstrated that HLA-DR molecules were present on OKT6- keratinocytes. The dermal infiltrate of psoriatic plaques contained T cells expressing the activation antigens, IL-2 receptor (Tac) and HLA-DR, as well as macrophages and OKT6+ cells. There was little difference in the characteristics of the dermal infiltrate between the lesions with or without HLA-DR+ keratinocytes. OKT6+ presumptive Langerhans cells were also found in the dermal infiltrates of patients with lichen planus, contact dermatitis, spongiotic dermatitis, erythema multiforme, basal and squamous cell carcinoma. Studies of keratinocyte suspensions showed that 7-84% of keratinocytes were HLA-DR+. Flow cytometry experiments showed that keratinocytes at all stages of differentiation were HLA-DR+. However, the stem cell-enriched population contained the highest proportion of HLA-DR+ cells. HLA-DR expression by keratinocytes correlated with disease activity. The expression was reversible with successful medical therapy. HLA-DR+ keratinocytes may activate T cells directly or may present an as yet unknown antigen to T cells. These studies provide further support for the hypothesis that immunological mechanisms play an important role in the pathogenesis of psoriasis.     

miR-125b inhibits keratinocyte proliferation and promotes keratinocyte apoptosis in oral lichen planus by targeting MMP-2 expression through PI3 K/Akt/mTOR pathway

Oral lichen planus (OLP) is a chronic inflammatory mucosal disease that involves the degeneration of keratinocytes. However, the etiology and mechanisms of OLP pathogenesis have not been fully elucidated. In this study, we used keratinocytes HaCaT stimulated with lipopolysaccharide (LPS) to mimic a local OLP immune environment, and investigated the regulatory role of miR-125b in keratinocyte proliferation and apoptosis under OLP conditions. Immunohistochemical analysis and quantitative real-time PCR (qRT-PCR) assay showed that MMP-2 expression was up-regulated and miR-125b expression was down-regulated in both OLP mucosa tissues and LPS-incubated HaCaT cells. Western blot analysis indicated that miR-125b overexpression suppressed LPS-induced MMP-2 expression in HaCaT cells. Molecularly, our results confirmed that MMP-2 is a target gene of miR-125b in HaCaT cells. The effect of miR-125b on cell proliferation was revealed by CCK-8 assay, BrdU assay and cell cycle analysis, which illustrated that miR-125b overexpression impeded LPS-induced HaCaT cell proliferation. Flow cytometry analysis further demonstrated that miR-125b overexpression promoted HaCaT cell apoptosis. Moreover, these effects were involved in PI3 K/Akt/mTOR activation, as miR-125b overexpression inhibited LPS-enhanced expression of p-Akt and p-mTOR proteins. Taken together, these data confirm that miR-125b might inhibit keratinocyte proliferation and promote keratinocyte apoptosis in OLP pathogenesis by targeting MMP-2 through PI3 K/Akt/mTOR pathway.     

脓毒症患儿CD4+CD25+调节性T细胞的变化

目的 观察不同免疫状态下脓毒症婴幼儿外周血CD4+CD25+Foxp3high调节性T细胞(Treg细胞)及相关分子的变化,探讨婴幼儿脓毒症免疫功能紊乱的可能机制.方法 分别收集2007年5月至2007年11月深圳市儿童医院重症监护室收治的婴幼儿脓毒症36例血液标本,另选16例健康同龄儿童作为正常对照进行前瞻性研究;排除既往患有自身免疫性疾病、免疫缺陷病、遗传代谢病及肿瘤的患儿,排除近6个月曾使用影响免疫功能的药物.本研究获得深圳市儿童医院伦理委员会的同意.以外周血CD14+单核细胞HLA-DR表达>30%或<30%为阈值,将患儿分为免疫激活组(DR-H组)和免疫抑制组(DR-L组),用流式细胞术检测CD14+单核细胞HLA-DR表达率,CD4+CD25+Foxp3highTreg细胞比例;实时荧光定量PCR(Real time-PCR)检测CD4+T细胞Foxp3、CTLA-4、GITR、IL-10mRNA表达.统计方法采用单因素方差分析,P<0.05为差异具有统计学意义.结果 急性期DR-L组CD4+CD25+Foxp3highTreg细胞比例明显高于对照组及DR-H组(P<0.05).DR-L组Foxp3、CTLA-4、IL-10等相关分子基因表达高于对照组及DR-H组(P<0.05),DR-L组GITR基因表达高于DR-H组.结论 CD4+CD25+Foxp3highTreg细胞数量异常增加可能与婴幼儿脓毒症免疫抑制状态有关.     

Effect of HLA-DR positive thyrocytes on in vitro thyroid autoantibody production

The function of HLA-DR positive thyrocytes on thyroid autoantibody production has been examined to test the hypothesis that such HLA-DR positive thyrocytes may initiate or aggravate autoimmune thyroid disease. Thyrocytes were cultured (precultured) with leucoagglutinin (which stimulated thyrocyte expression of HLA-DR, beta 2-microglobulin (beta 2-m) and thyroid microsomal antigens) and then cocultured with peripheral blood mononuclear cells. Thyroid antibody production by the latter was then measured. There was no evidence of induction or enhancement of thyroid-microsomal and thyroglobulin autoantibody production in supernatants from the cocultures of autologous peripheral blood mononuclear cells and HLA-DR positive thyrocytes from normal controls and patients with Graves' disease. Furthermore, stimulation of B lymphocytes from patients with autoimmune thyroid disease with a combination of Staphylococcus aureus Cowan I plus supernatants from autologous cocultures of peripheral blood mononuclear cells and HLA-DR positive thyrocytes from normal controls and Graves' disease, produced significantly less microsomal antibody and thyroglobulin antibody than similar cocultures with HLA-DR negative thyrocytes, although total immunoglobulin G (IgG) was similar in both groups. The effect of supernatants from allogeneic cocultures on microsomal antibody thyroglobulin antibody and total IgG production was no different between HLA-DR positive and HLA-DR negative thyrocytes. These data suggest that HLA-DR positive thyrocytes may have a protective role against thyroid autoimmunity rather than a pathogenic role for it.     

丹参饮合生脉散治疗不稳定性心绞痛

目的：研究丹参饮合生脉散对不稳定性心绞痛的治疗作用。方法：将１１８例患者随机分为丹参饮合生脉散组（治疗组７８例）和西药常规治疗组（对照组４０例）。治疗组在西药常规治疗的基础上加服中药丹参饮合生脉散。观测２组患者心绞痛症状，心电图变化，硝酸甘油消耗量及中医各证型疗效等。结果：２组心绞痛症状疗效比较有显著性差异（Ｐ＜０．０５）；２组心电图疗效比较有显著差异（Ｐ＜０．０５），治疗组疗效优于对照组；硝酸甘油消耗量治疗后较治疗前２组均明显减少（Ｐ＜０．００１或Ｐ＜０．０１）；硝酸甘油停减率治疗组比对照组提高了１０．４５％，但无统计学意义（Ｐ＞０．０５）。治疗组中气虚血瘀型疗效最好，痰湿阻滞型最差，两证型比较有显著差异（Ｐ＜０．０５），其它各证型之间疗效无显著差异（Ｐ＞０．０５）。结论：丹参饮合生脉散治疗不稳定性心绞痛确有一定的疗效，中西药合用有一定的协同作用和优势     

Circulating regulatory anti-T cell receptor antibodies in patients with myasthenia gravis

Serum anti-T cell receptor (TCR) Ab's are involved in immune regulation directed against pathogenic T cells in experimental models of autoimmune diseases. Our identification of a dominant T cell population expressing the Vbeta5.1 TCR gene (TCRBV5-1), which is responsible for the production of pathogenic anti-acetylcholine receptor (AChR) autoantibodies in HLA-DR3 patients with early-onset myasthenia gravis (EOMG), prompted us to explore the occurrence, reactivity, and regulatory role of anti-TCR Ab's in EOMG patients and disease controls with clearly defined other autoantibodies. In the absence of prior vaccination against the TCR, EOMG patients had elevated anti-Vbeta5.1 Ab's of the IgG class. This increase was restricted largely to EOMG cases with HLA-DR3 and with less severe disease, and it predicted clinical improvement in follow-up studies. EOMG patient sera containing anti-TCR Ab's bound specifically the native TCR on intact Vbeta5.1-expressing cells and specifically inhibited the proliferation and IFN-gamma production of purified Vbeta5.1-expressing cells to alloantigens in mixed lymphocyte reaction and the proliferation of a Vbeta5.1-expressing T cell clone to an AChR peptide, indicating a regulatory function for these Ab's. This evidence of spontaneously active anti-Vbeta5.1 Ab's in EOMG patients suggests dynamic protective immune regulation directed against the excess of pathogenic Vbeta5.1-expressing T cells. Though not sufficient to prevent a chronic, exacerbated autoimmune process, it might be boosted using a TCR peptide as vaccine.     

Comparison of platelet immunity in patients with SLE and with ITP

Idiopathic thrombocytopenic purpura (ITP) is characterized by the development of a specific anti-platelet autoantibody immune response mediating the development of thrombocytopenia. Systemic lupus erythematosus (SLE) is an autoimmune disease characterized by the production of a wide variety of autoantibodies. In 15-20% of SLE cases, patients develop thrombocytopenia which appears to be autoimmune in nature (SLE-TP). To better understand the pathogenesis of the thrombocytopenia associated with SLE, we investigated the overlapping platelet and cellular immune features between SLE and ITP. Thirty-one patients with SLE, eight with SLE-TP, and 17 with ITP, were studied and compared to 60 healthy controls. We evaluated platelet-associated IgG, platelet microparticles, reticulated platelets, platelet HLA-DR expression, in vivo cytokine levels, lymphocyte proliferation, and the T lymphocyte anti-platelet immune response in these patients. Patients with SLE-TP and those with ITP had increased platelet-associated IgG, an increased percentage of platelet microparticles, a higher percentage of reticulated platelets and larger platelets, suggesting antibody-mediated platelet destruction and increased platelet production. More than 50% of patients with ITP had increased HLA-DR on their platelet surface whereas subjects with SLE-TP did not. Analysis of serum cytokines demonstrated increased levels of IL-10, IL-15 and TNF-alpha in patients with SLE, but in those with ITP, only increased levels of IL-15 were seen, no increases in any of these cytokines were observed in patients with in SLE-TP. The ability of lymphocytes to proliferate in response to phorbol myristate acetate (PMA) stimulation was increased in SLE-TP, but was normal in both SLE and ITP. Lymphocytes from subjects with ITP displayed an increased ability to proliferate on exposure to platelets, in contrast, those with SLE-TP did not. While the number of subjects evaluated with SLE-TP was small, these data reveal a number of differences in the immunopathogenesis between SLE-TP and ITP.     

Lichen planus and hepatitis C virus in the Northern Kyushu region of Japan

Abstract. Oral lichen planus (OLP) is a common oral disorder that manifests a mucosal reaction to a variety of aetiological factors, including liver disorder. This study investigated the relationship between OLP and hepatitis C virus (HCV) infection by studying the prevalence of hepatitis B and C virus infection or liver disease in 45 patients with OLP in the Northern Kyushu region of Japan where the prevalence of HCV infection is the highest in the country. Serum hepatitis B virus surface antigen (HBsAg) was positive in only four patients. Serum anti-HCV or serum HCV RNA was positive in 28 (62%) and 27 (60%) of 45 OLP patients, respectively. The majority (35 of 45, 78%) of OLP patients suffered from liver disease, including chronic hepatitis C (22/45, 49%), HCV-related liver cirrhosis (two), and HCV-related hepatocellular carcinoma (two). These results suggest that HCV is a major cause of OLP.