【作者】 魏春波；

【导师】 董萍云；

【作者基本信息】 河北医科大学 ， 皮肤病与性病学， 2004， 硕士

【摘要】 目的：近年来，关于荨麻疹的发病机制的研究取得了较大进展，一般认为荨麻疹的发病机制有变态反应性和非变态反应性两种，其中Ⅰ型变态反应是荨麻疹的主要发病机制。近年来有学者提出T辅助细胞亚群（Th1与Th2）功能失衡与过敏性皮肤病发病密切相关。而IL-4（白细胞介素－4）是Th2细胞分泌的主要的细胞因子，有研究表明慢性荨麻疹患者IL-4血清学水平明显高于正常对照组，并且PBMC（外周血单个核细胞）体外产生IL-4的水平也明显增高，说明IL-4在过敏性疾病的发生、发展中起着重要作用。VCAM-1（血管细胞黏附分子－1）属于黏附分子的免疫球蛋白超家族，主要表达于血管内皮细胞，受多种炎症因子和细胞因子的影响，活化血管内皮细胞可释放sVCAM-1（可溶性血管细胞黏附分子－1）。 sVCAM-1是VCAM-1胞外区的大部分序列，被认为是膜分子脱落形成。有研究表明，荨麻疹患者VCAM-1水平可反映疾病的病情变化，这对于监测病情和疗效判断具有较大的临床意义。在临床上慢性荨麻疹（chronic urticaria）发病率较高，为皮肤科常见疾病，其病因比较复杂，药物治疗有效，但停药后易复发，因此慢性荨麻疹的治疗是临床医师面临的一个很棘手的问题。而特异性免疫治疗以副作用小、疗效持久显示出一定的优势。关于特异性免疫治疗<WP=4>的机制，人们曾提出“封闭抗体”、“消耗理论和微休克理论”、“胸腺抑制细胞反馈学说”等多种学说。也有学者认为特异性免疫治疗并不能完全解除患者对保留过敏原的敏感状态，而是通过提高机体对致敏物的耐受能力而达到治疗目的。特异性免疫治疗是对已被某种过敏原致敏的机体通过一定的途径，连续、小量、多次给予过敏原，使机体对其致敏性逐渐降低以至脱敏，当再次遇到该过敏原时不再发生过敏反应。因此，对那些能检出而难以避免接触的过敏原可以采取该方法，具有治疗和预防的双重意义。特异性免疫治疗作用机理虽然至今尚未完全清楚，但其作用疗效得到公认。然而，特异性免疫治疗周期较长，至今仍无客观的实验室指标进行病情的监测和疗效的判定。本实验采用特异性免疫治疗慢性荨麻疹患者，观察疗效并检测治疗前后血清中IL-4、sVCAM-1水平变化。一方面试图从临床与血清学指标两方面来评价特异性免疫治疗的治疗效果，另一方面观察特异性免疫治疗对IL-4、sVCAM-1水平的影响，以进一步探讨特异性免疫治疗的作用机理，为临床提供可靠的客观依据。材料与方法：病例组：来自2002年10月至2003年12月河北医科大学第二医院皮肤科门诊，共30例。所有患者均为临床症状典型的慢性荨麻疹患者，表现为风团时多时少，反复发生，病程常达数月或数年。排除红斑狼疮、天疱疮、皮肌炎、风湿性关节炎等自身免疫性疾病以及肿瘤和其他严重系统疾患及其他过敏性疾病，并且就诊前3天未曾服抗组胺制剂、1个月内未服用息斯敏以及2个月内未用糖皮质类固醇激素和免疫抑制剂等影响全身免疫功能的药物，并且经过敏原皮肤试验（吸入性变应原）阳性患者。对照组：<WP=5>来自本院健康查体人员，共20例，均无过敏性疾患和自身免疫性疾病及家族史。病例组检测过敏原阳性后，给予特异性免疫治疗，5周为1疗程，连续3个疗程。分别记录治疗前后患者的皮疹、自觉症状等，进行评分并计算症状积分下降指数（SSRI）：基本痊愈≥90％，显效60％≤SSRI<90%，微效30％≤SSRI<60%，无效SSRI<30%（无变化或加重）。并于治疗前后采集患者静脉血4毫升，分离血清，采用ELISA法检测血清中IL-4、sVCAM-1浓度，具体操作严格按照试剂盒说明进行。结果：1、病例组治疗3个疗程后，基本痊愈8例，显效17例，微效3例，无效2例，有效率为83.33％；2、血清中IL-4浓度测定结果（单位 pg/ml）病例组平均值为48.157±33.523明显高于正常对照组（31.223±15.477）（P<0.05）。治疗以后病例组IL-4平均值为34.240±18.218，与治疗前相比，有显著差异（P<0.01）。3、血清中sVCAM-1的测定结果（单位：ng/ml）：病例组平均值为2014.03±1095.95，明显高于正常对照组(1148.41±872.98)（P<0.01）。治疗以后病例组sVCAM-1平均值为1409.57±904.46， 与治疗前相比，有显著差异（P<0.001）。4、IL-4与sVCAM-1经过直线相关分析无相关性（r=0.0268）（P>0.05）。结论：本实验采用特异性免疫治疗治疗慢性荨麻疹患者30例，观察临床疗效并用ELISA法检测治疗前后患者血清中IL-4、sVCAM-1水平。得出以下结论：1、特异性免疫治疗对慢性荨麻疹安全有效。2、血清中IL-4、sVCAM-1水平与慢性荨麻疹患者的病情变化密切相关，可作为检测病情、疗效判断的客观指标。3、经直线相关分析，血清中IL-4与<WP=6>sVCAM-1水平无相关性。4、特异性免疫治疗可能是通过TH1/TH2调节免疫系统和降低黏附分子的产生减少从而肥大细胞和嗜碱粒细胞的局部聚集而发挥治疗作用的。更多还原

【Abstract】 Objective: In recent years, the study about the pathogenesis of chronic urticaria was made great progress. Generally, urticaria can be classified by pathogenesis: immunologic, and nonimmunologic. Most of immunologic pathogenesis is IgE-dependent, type I hypersensitivity. Some studies indicated that the function of T helper cell subpopulation is unbalanced, which lead to allergy diseases, and that Interleukin-4 (IL-4) secreted by the PBMC (peripheral blood mononuclear cells) which were cultured in vitro with phytohemagglutinin(PHA) in chronic urticaria patients were significantly higher than in normal controls. The serum level of IL-4 is found higher than normal controls in studies. Many studies showed that IL-4 is the key factor in the allergy diseases. Vascular adhesion molecule-1 (VCAM-1) belongs to immunoglobulin superfamily. In normal case, it express lowly on the surface of vascular cells and lymphocytes. Soluble vascular adhesion molecule-1 (sVCAM-1) has the most alignment of VCAM-1, it is separated from the membrane. Recent evidence indicated that the level of VCAM-1 could reflect the disease activity and response to treatment. The <WP=8>incidence rate of chronic urticaria is high, and drug treatment is effective but easy to relapse. Specific immunotherapy is super to drug treatment for its persistent effect and little side effect, however its mechanism is unclear. We treated 30 patients with chronic urticaria with specific immunotherapy, having observed the effect and measured the serum levels of IL-4 and sVCAM-1 before and after treatment. Our purpose is to evaluate the effect of specific immunotherapy objectively and accurately, at the same time observe the affection of specific immunotherapy to the serum levels of IL-4 and sVCAM-1, further to research the mechanism of specific immunotherapy, thereby provide evidence to clinic therapy for chronic urticaria. Materials and methods: 30 patients with chronic urticaria were collected from the dermatology department of the Second Affiliated Hospital of Hebei Medical University from 2002.10 to 2003.12. All patients were classic chronic urticaria, excluded SLE, pemphigus, dermtomyositis, autoimmune diseases and other allergy diseases. Any drugs affected immune function had not used in recent 2 months. 20 healthy persons were taken as normal controls. Specific immunotherapy was taken by patient group for more than 3 months. We recorded the score of clinic symptom before and after treatment. At the same time, we collected 4 ml blood from patients, separated serum, and measured the levels of IL-4, sVCAM-1 by ELISA. Results: 1. After treatment, most patients symptom remitted, the SSRI (symptom score reduce index) decreased <WP=9>significantly. The effective rate was 83.33%, and no side effect was found. 2. The serum level of IL-4 in chronic urticaria patients (average 48.157±33.523pg/ml) was significantly increased compared to normal controls (average 31.223±15.477pg/ml)(P<0.05). After treatment, the serum level of IL-4 in chronic urticaria patients decreased significantly(average 34.240±18.218pg/ml) (P<0.01). 3. The serum level of sVCAM-1 in chronic urticaria patients (average 2014.03±1095.95ng/ml) was significantly increased compared to normal controls (average 1148.41±872.98ng/ml)(P<0.01). After treatment, the level of sVCAM-1 in chronic urticaria patients decreased significantly (average 1409.57±904.46ng/ml)(P<0.001). 4. In chronic urticaria patients, there was no significant correlation between the serum level of sVCAM-1 and IL-4 (P<0.05). Conclusions: Our results proved that specific immunotherapy is an effective and safe therapy for chronic urticaria. Our findings showed that the serum level of IL-4 and sVCAM-1 was reduced with the SSRI decreasing, which suggested that IL-4 and sVCAM-1 may be used as a maker for monitoring disease activity and response to treatment in chronic urticaria. In chronic urticaria patients, there was no significant correlation between the serum level of sVCAM-1 and IL-4. Above findings, it was indicated that spe更多还原