荨麻疹的病理生理与临床

一直以来,荨麻疹的发生被认为是肥大细胞膜表面高亲和力IgE受体（FceRI）发生交联．引发肥大细胞脱颗粒释放组胺等介质所致。然而,新近研究提示,Ⅰ-Ⅳ型变态反应及非免疫机制均可介导肥大细胞活化。肥大细胞活化后发生脱颗粒、合成炎症因子和脂类代谢物等3个既相对独立又相互关联的事件,共同决定荨麻疹的发生、发展。正确认识荨麻疹的病理生理,有助于深入理解荨麻疹临床表现的多样性,指导临床规范有序地开展过敏原检测,并为治疗提供新的理念。[第一段]     

肥大细胞释放组胺机制的研究进展

肥大细胞释放组胺在变态反应和非变态反应发病机制中均起重要作用.研究表明,肥大细胞主要通过免疫学途径和非免疫学途径释放组胺,多种物质参与组胺释放过程.特异性IgE介导肥大细胞释放组胺是肥大细胞激活的典型方式.抗FcεRI抗体和抗IgE抗体在慢性特发性荨麻疹肥大细胞释放组胺机制中起作用.凝血机制中生成的凝血酶可激活蛋白酶激活受体,介导肥大细胞黏附于纤维连接蛋白,诱发肥大细胞释放组胺.遗传因素、神经精神因素及物理因素也参与荨麻疹患者肥大细胞释放组胺.     

自身免疫性荨麻疹

自身免疫性荨麻疹是指功能性自身抗体通过与高亲和性IgE受体(FcεRI)交联,激活肥大细胞和嗜碱性粒细胞释放组胺而引起的荨麻疹.诊断主要依据临床表现、自体血清皮肤试验、嗜碱性粒细胞释放组胺活性的检测,以及器官特异性自身抗体的检测.一线治疗可口服抗组胺药物,疗效不佳者可应用糖皮质激素,严重患者可考虑使用免疫抑制剂、静脉注射用人免疫球蛋白,也可采用血浆置换等治疗.     

奥马珠单抗治疗慢性自发性荨麻疹的进展

【摘要】 慢性自发性荨麻疹指不明原因反复发作风团超过6周,伴或不伴血管神经性水肿。其发病的中心环节是肥大细胞和嗜碱性粒细胞激活、脱颗粒。奥马珠单抗是一种人源化、重组单克隆IgG抗体,能选择性结合游离IgE抗体Fc段,阻断IgE?FCεRⅠ轴所引起的肥大细胞、嗜碱性粒细胞激活。已发布评价奥马珠单抗治疗慢性自发性荨麻疹的Ⅲ期临床试验有3项,证实了奥马珠单抗在治疗难治型慢性自发性荨麻疹的有效性和安全性。     

嗜碱性粒细胞在慢性自发性荨麻疹发病及治疗预测中的作用

嗜碱性粒细胞在慢性自发性荨麻疹(CSU)等变态反应性炎症中发挥着不可替代的作用.过敏反应期间,嗜碱性粒细胞以IgE依赖或非IgE依赖的方式被激活,细胞内外信号转导调节发生异常,释放组胺、IL-4、IL-13、血小板活化因子(PAF)等效应分子,组织中的趋化因子促进嗜碱性粒细胞向外周组织募集,使得外周血嗜碱性粒细胞减少....     

慢性自发性荨麻疹发病机制的研究进展

慢性自发性荨麻疹(chronic spontaneous urticaria,CSU)是指皮肤出现风团伴瘙痒几乎每天发生并持续6周以上伴或不伴血管性水肿者。CSU发病可由免疫和非免疫介导,其中免疫介导以T细胞、B细胞和补体为主,非免疫介导以激活肥大细胞脱颗粒为基础。T细胞主要通过分泌细胞因子激活和/或招募靶细胞参与CSU发病过程中的自身免疫。由IgE介导的Ⅱ型变态反应只见于30%CSU,IgG介导的Ⅲ型变态反应构成了血清病型CSU发病的基础。凝血与抗凝血系统参与CSU发病的可能机制是凝血途径被激活后,产生凝血酶。凝血酶作为一种蛋白酶激活受体激动剂,诱导肥大细胞释放组胺。肥大细胞被激活释放组胺的过程有时还需要补体的参与。有人提出幽门螺杆菌感染与甲状腺自身抗体参与CSU的发病,而作用机制尚存争论。本文就目前CSU发病机制的研究进展作一综述。     

Ⅰ型变态反应的特异性体外检测

体外检测Ⅰ型变态反应有安全、量化、受药物干扰小的特点.目前常用的特异性IgE检测的检验效能差异较大.细胞介质释放试验可用于IgE介导和非IgE介导的疾病,包括组胺释放试验、半胱氨酰白三烯释放试验、纤溶酶释放试验、15-羟基廿碳四烯酸释放试验等,但是检验效能相对较低.流式细胞仪下的嗜碱粒细胞活化试验,可以用于IgE介导和非IgE介导的变态反应,并且检验效能比细胞介质释放试验高.     

慢性荨麻疹部分发病机制的研究进展

慢性荨麻疹是临床常见的一种反复发作的过敏性疾病,其发病机制除了肥大细胞脱颗粒释放组胺以外,还有IgE及其受体的自身抗体FcεRI引发的自身免疫反应、Th1/Th2细胞亚群失衡,以及炎症递质白三烯释放所导致的后续炎症反应等参与.这些异常免疫反应将给那些难以单纯用抗组胺药物治疗的慢性荨麻疹带来更多的治疗靶位.     

慢性自发性荨麻疹的发病机制研究进展

慢性自发性荨麻疹(chronic spontaneous urticaria,CSU)是指无诱因、反复发作、病程持续6周以上的皮肤、黏膜瘙痒性风团疹和/或血管性水肿。肥大细胞和嗜碱性粒细胞是CSU发病的关键效应细胞,但其活化的方式及释放的介质有所差别。自身免疫、肥大细胞和嗜碱性粒细胞信号失调、凝血以及氧化应激都参与了CSU的发病,且这些机制之间存在相互串扰、相互激活的关系。     

荨麻疹

20060237嗜碱性粒细胞组胺释放试验检测原发性获得性寒冷性荨麻疹患者血清组胺释放活性/彭少文(三军大西南医院皮肤科),郝飞,钟白玉…∥免疫学杂志.-2005,21(3).-223~225通过分离人外周血嗜碱性粒细胞,进行体外组胺释放实验,测定组胺释放率。结果15例原发性获得性寒冷性荨麻疹(     

Physiopathology of urticaria

Urticaria is a common disorder that affects as many of 20% of all people at sometime during their lives. It is a cutaneous reaction pattern for which there are multiple potential causes. Its physiopathology is poorly defined. The vascular changes observed in urticarial lesions can be attributed to the release of mediators: histamine plays an essential role but others mediators, such as serotonin, eicosanoids, kinins, neuropeptides. may also be involved. These mediators are synthetized by mast cells which are the major effector cell type. However, other cells, basophils, mononuclear cells, platelets, endothelial cells have also been implicated. During immediate hypersensitivity reaction, mast cells and basophils are activated by allergens through cross linking of cell-surface-bound IgE. However, more often than not, these cells are stimulated by non-immunological mechanisms. At present, some data are better understood: in urticaria, there is a late phase reaction which involves cytokines and cell adhesion molecules. Recent work has also demonstrated the role of circulating functional histamine - releasing auto antibodies that bind to the high affinity IgE receptor (FcepsilonRI) or, less commonly, to IgE. As the pathophysiological mechanisms responsible for urticaria are better defined, therapeutic agents other than H1 histamines, should be available.     

凝血机制参与慢性荨麻疹发病的研究进展

凝血机制与慢性荨麻疹有关.内外凝血途径均参与其发病,同时被激活产生凝血酶.凝血酶不仅可以直接作用于血管内皮细胞,增加血管通透性,还可以间接使肥大细胞脱颗粒释放组胺,从而诱发荨麻疹.慢性荨麻疹患者检测出的一些凝血标记物也间接证明凝血机制参与其发病.在慢性荨麻疹发病过程中,凝血机制与炎症反应机制、自身免疫机制和血管机制密切相关.对于抗组胺治疗无效的顽固性荨麻疹患者,抗凝血治疗提供了新的思路和方向.     

Histamine: The Quintessential Mediator

Histamine is unique in being the only substance described to date which fulfils all of the criteria established by Dale for an inflammatory mediator. Thus, histamine is known to cause the “Triple Response” of Lewis and to act via H₁ and H₂ receptors to produce vasodilation and increased vascular permeability; elevated levels of histamine are found in inflamed tissue; histamine is produced and stored in mast cells and mere are established mechanisms for histamine release via mast cell surface receptors; and antihistamines alleviate the clinical manifestations of histamine release. There have been several recent advances in our understanding of histamine pharmacology and of the pathomechanisms of chronic idiopathic urticaria (CIU), a disease in which histamine plays an important role. Two new histamine receptors have been identified, the inhibitory (H₃) receptor and the intracellular (H_ic) receptor involved in cell proliferation. There is now evidence that mast cell derived histamine release in patients with CIU is due to an autoimmune disease, mediated by autoantibodies to the α-subunit of the high affinity IgE receptor on mast cells and basophils. Removal of these autoantibodies by plasmapheresis, or treatment with intravenous immunoglobulins may cause clinical remission. Cyclosporin A has also been found to be of benefit to some patients with CIU probably due to a mast cell “stabilising” effect, leading to reduced release of histamine and other mediators. This article reviews our current knowledge on histamine, its role, receptors and mechanisms for release.     

免疫球蛋白E型自身抗体在自身免疫相关皮肤病中的研究进展

【摘要】 大量研究显示,免疫球蛋白E（IgE）不但参与变态反应的发生发展,还可通过多种机制诱发和加重自身免疫反应。IgE型自身抗体已证实可在多种自身免疫相关皮肤病中出现,可能通过与自身抗原结合影响树突细胞、肥大细胞、嗜碱性粒细胞等多种免疫机制参与相关疾病的发生发展。本文综述IgE在系统性红斑狼疮、大疱性类天疱疮以及慢性特发性荨麻疹等自身免疫相关皮肤病的诱发和加重中所起的作用和可能机制,为临床诊治提供理论基础。     

Histamine release from skin mast cells and basophils in patients with urticaria pigmentosa.

Histamine release from dispersed skin mast cells may be used for functional studies on the mast cell. However, technical difficulties have hampered such studies. In the present study a new fiberglass-based histamine assay was applied to previously described dispersion techniques, using excision biopsies from 7 patients with urticaria pigmentosa, 3 with psoriasis as well as 4 with urticaria. However, sufficient mast cell numbers for performing histamine release could only be obtained from patients with urticaria pigmentosa. The average mast cell yield was 935 +/- 470 cells (mean +/- SD) per mg wet weight of tissue. The skin mast cells from these patients responded with dose-dependent histamine release to anti-IgE, calcium ionophore A23187, and N-formyl-methionyl-leucyl-phenylalanine challenge without previous passive sensitization. The pattern of histamine release of mast cells and corresponding blood basophils did not indicate substantial differences between the two cell types.     

Urticaria. An updated review.

Urticaria can result from many different stimuli, and numerous factors, both immunologic and nonimmunologic, are involved in its pathogenesis. Most commonly considered of immunologic mechanisms is the type I hypersensitivity state mediated by IgE. Another immunologic mechanism involves the activation of the complement cascade, which produces anaphylatoxins that can release histamine. Immunologic, nonimmunologic, genetic, and modulating factors converge on mast cells and basophils to release mediators capable of producing urticarial lesions. In addition to the clinical and laboratory diagnosis and treatment regimens, we review such mediators as histamine, kinins, serotonin, slow-reacting substance of anaphylaxis, prostaglandins, acetylcholine, fibrin degradation products, and anaphylatoxins that increase vascular permeability and can thereby produce wheals. Special consideration is given to histamine and the factors that regulate is secretory release from mast cells and basophils, including the modulating role of intracellular levels of cyclic adenosine monophosphate.     

维生素D与慢性荨麻疹的研究进展

慢性荨麻疹患者的平均维生素D与对照组相比明显偏低,且与病情严重程度及病程存在负相关.尽管尚不明确其中的因果关系,两者间的潜在联系可能与维生素D所起的免疫调节作用有关.有研究表明,维生素D可通过结合维生素D受体影响下游信号通路及核内转录水平,从而对肥大细胞、淋巴细胞以及嗜酸性粒细胞等多种免疫细胞的功能产生调节效应.维生素D可抑制肥大细胞释放活性介质,还可影响T淋巴细胞亚群动态平衡和迁移,引起干扰素γ水平下降和白细胞介素10水平升高等变化,可能是维生素D影响荨麻疹发病的重要机制.同时,临床药物试验显示,补充维生素D对慢性荨麻疹的治疗具有潜在的辅助作用.因此,若能继续明确维生素D与慢性荨麻疹发病的因果关系,从细胞及基因层面研究维生素D对肥大细胞等主要效应细胞的具体影响,将有助于为慢性荨麻疹的诊断和治疗找到新的理论依据.     

Neue Therapieoptionen der Urtikaria und ihrer Subtypen

Urticaria is one of the most common skin diseases. It is divided into several categories including acute and chronic urticaria as well as physical urticaria and special subtypes such as cholinergic and autoimmune urticaria. The causes of urticaria are multiple. In more than 80%, urticaria is triggered by an inflammatory focus, a subclinical infection or autoimmune actions. In addition, non-specific pharmacological or toxin-mediated release of inflammatory mediators from basophils or mast cells can also trigger urticaria. These new aspects in the pathophysiology of urticaria suggest new and promising therapeutic strategies. The first line treatment of urticaria still consists of non-sedating H1-antihistamines. Since urticaria has a profound impact on quality of life, effective treatment is very important. We consider new therapeutic options based on our long-term experience in treating patients with urticaria.     

Not all chronic urticaria is "idiopathic"

Abstract: The aetiology of chronic urticaria in the majority of patients is elusive. The cause of physical urticarias (dermographism, delayed pressure urticaria, cold urticaria) is unkonown. We have identified a subset of chronic "idiopathic" urticaria patients, representing approximately 30% of the total in which the disease is caused by the presence of IgG autoantibodies against the high affinity IgE receptor (FcœRIα). This functional autoantibody stimulates normal (albeit vicarious) activation of mast cells and basophils via FcœRI, causing whealing and angioedema. Anti-FcœRI-positive patients are recognized by a combination of autologous serum skin testing and evoked histamine release from basophils of normal human donors. Autoantibody-positive and -negative patients are clinically indistinguishable and are treated routinely by combinations of H₁ and occasionally H₂-antihistamines in both cases. However, severely affected patients who are anti-FcœRI-positive can also be treated by non-specific immunotherapy (plasma pheresis, intravenous immunoglobulin, cyclosporin.     

组胺和抗组胺药的研究进展

组胺与H1受体结合可增强抗原提呈细胞的能力,促进肥大细胞和嗜碱性粒细胞中组胺和其他介质的释放,在荨麻疹等过敏性疾病的发病中起着作用。第一代川抗组胺药由于相对分子质量小,嗜脂性,易通过血脑屏障,临床应用可产生较多不良反应,尤其是对警觉性、认知等的影响。第二代H1抗组胺药相对分子质量大,受体专一性强、亲和力高,抗组胺活性更强,安全性更好,国外指南均推荐作为荨麻疹的一线治疗药物,治疗剂量可增至标准剂量的4倍以提高疗效,仍具有很好的安全性。H3、H4抗组胺药也已进入临床试验,有望治疗过敏性疾病及瘙痒症。