EXPERIMENTAL APPROACHES TO SPECIFIC IMMUNOTHERAPIES IN AUTOIMMUNE-DISEASE - FUTURE TREATMENT OF ENDOGENOUS POSTERIOR UVEITIS
EXPERIMENTAL APPROACHES TO SPECIFIC IMMUNOTHERAPIES IN AUTOIMMUNE-DISEASE - FUTURE TREATMENT OF ENDOGENOUS POSTERIOR UVEITIS
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DOI：
10.1136/bjo.79.1.81
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发表时间：
1995-01-01
影响因子：
4.1
通讯作者：
DICK, AD
中科院分区：
文献类型：
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作者：
DICK, AD
（自身）免疫介导的疾病是多种多样的，几乎可以影响任何器官。在过去，它们的治疗主要是非特异性免疫抑制，并在控制疼痛方面得到止痛剂和非甾体抗炎剂的支持，例如在类风湿性关节炎中。类固醇和细胞毒性药物免疫抑制的副作用，对于任何疾病的控制都必须长期服用，通常超过任何治疗的益处。然而，在过去的二十年中，更特异性的免疫抑制剂的发现，例如，环孢菌素A（CsA），以及对潜在免疫过程（例如，T细胞活化，T细胞受体，细胞因子）的进一步理解，导致了对免疫介导疾病的特异性治疗的兴趣。较新的免疫抑制疗法旨在通过短期治疗和对所需抗原的特异性来长期抑制（自身）免疫反应。内源性后葡萄膜视网膜炎（EPU）是公认的（自身）免疫性疾病的最佳眼部例子之一。然而，对于什么是EPU仍然存在冲突。EPU的特征在于离散临床体征的组合，包括炎性细胞的玻璃体浸润（玻璃体炎）、白细胞的局灶性或弥漫性脉络膜视网膜浸润（脉络膜炎）、视网膜内外血管炎症（视网膜血管炎）以及黄斑和视神经乳头水肿。从这些症状的组成部分中产生了大量的临床病症，包括交感性眼炎、中间葡萄膜炎、鸟射性脉络膜视网膜炎和色素上皮炎。尽管这些疾病的表现、HLA相关程度和对相对非特异性治疗的反应各不相同，但临床和实验模型中越来越多的证据表明，这些疾病的特征是过度的免疫反应，导致组织破坏，并且没有明显的感染病因，可能是自身免疫性的（表1）。产生的免疫机制要么是针对自身抗原，要么是作为一种反应触发的，例如，由感染因子（即外来抗原），这可能与宿主抗原显示出一定的同源性，并产生交叉反应（分子模拟）。炎症反应被成功抑制的时间点取决于免疫反应是针对进入组织的宿主抗原还是外来抗原。无论哪种方式，当没有发现明显的感染或肿瘤病因时，治疗可以针对抑制所产生的炎症级联反应，并有望减少组织损伤。对于前者，我将讨论抑制特异性自身反应性T细胞的可能性，而不是抑制炎症介质
(Auto) immune mediated diseases are diverse and may affect almost any organ. In the past their treatment has been largely with non-specific immunosuppression and supported, in controlling pain, with analgesics and non-steroidal anti-inflammatory agents in, for example, rheumatoid arthritis. The side effects of immunosuppres-sion with steroids and cytotoxic agents, which for any control of disease have to be taken on a long term basis, often outweigh the benefits of any treatment. However, over the pasttwo decades the discovery of more specific immunosuppressive agents-for example, cyclosporin A (CsA), and the further understanding of underlying immune processes (for example, T cell activation, T cell receptors, cytokines) has led to a wave of interest in developing specific treatments for immune mediated diseases. Newer immunosuppressivetherapies are aiming to give long term suppression of (auto) immune responses with only short term treatment and specificity for the desired antigen.Endogenous posterior uveoretinitis (EPU) is one of the best ocular examples of putative (auto) immune disease. However, there is still conflict as to what constitutes EPU. EPU is characterised by a combination of discrete clinical signs which include vitreal infiltration with inflammatory cells (vitritis), focal or diffuse chorioretinal infiltration with leucocytes (choroiditis), inner and outer retinal vessel inflammation (retinal vasculitis), and macular and optic nerve head oedema. 1 2 From these building blocks of signs arises a large spectrum of clinical conditions including sympathetic ophthalmia, intermediate uveitis, birdshot chorioretinitis, and pigment epithelitis. Although these conditions vary in their presentation, degree of HLA asso-ciation, and response to relatively non-specific treatment, there is growing evidence both clinically and in experimental models that these conditions are characterised by an exaggerated immune response which causes tissue destruction and, without an obvious infective aetiology, is likely to be autoimmune in nature (Table 1). 3 4 The immune mechanisms generated are either directedtowards autoantigens or as a response triggered, for example, by an infectious agent (that is, foreign antigen), which may show some homology with host antigens and generate cross reactivity (molecular mimicry). The points at which the inflammatory response may be inhibited successfully would depend on whether the immune response was directed against host or foreign antigen which enters the tissue. Either way, when no overt infectious or neoplastic aetiology is found treatment may be directed towards dampening the resulting inflammatory cascade and hopefully reduce tissue damage. With the former I will discuss the possibility of inhibiting specific autoreactive T cells as opposed to inhibiting inflammatory mediators