ORAL ADMINISTRATION OF ANTIGEN AND THE OCULAR IMMUNE RESPONSE

口服抗原和眼部免疫反应

• 批准号: 9362362
• 负责人: Robert Nussenblatt
• 金额: $ 27.29万
• 依托单位: NATIONAL EYE INSTITUTE
• 依托单位国家: 美国
• 资助国家: 美国
• 起止时间: 至
• 项目状态: 未结题
• 来源: https://reporter.nih.gov/project-details/9362362
• 关键词: Adrenal Cortex Hormones; Age related macular degeneration; Animal Model; Antigens; Arrestins; Autoimmune Process; B-Lymphocytes; Blood group antigen S; Chronic; Clinical Trials; Collaborations; Color; Complex; Computational Technique; Cooperative Research and Development Agreement; Data; Development; Disease; Eye; HLA-B Antigens; Human; Immune response; Immunology; Immunosuppressive Agents; Inflammation; Inflammatory; Institutional Review Boards; Link; Masks; Oral; Oral Administration; Participant; Patients; Peptides; Pharmaceutical Preparations; Phase; Placebos; Prednisone; Prevention; Protocols documentation; Publications; Randomized; Rattus; Retinal; Safety; T-Lymphocyte; Testing; Therapeutic immunosuppression; Time; Toxic effect; United States National Institutes of Health; Uveitis; base; feeding; interstitial retinol-binding protein; oral tolerance; protein aminoacid sequence; treatment group; uveoretinitis; Adrenal Cortex Hormones; Age related macular degeneration; Animal Model; Antigens; Arrestins; Autoimmune Process; B-Lymphocytes; Blood group antigen S; Chronic; Clinical Trials; Collaborations; Color; Complex; Computational Technique; Cooperative Research and Development Agreement; Data; Development; Disease; Eye; HLA-B Antigens; Human; Immune response; Immunology; Immunosuppressive Agents; Inflammation; Inflammatory; Institutional Review Boards; Link; Masks; Oral; Oral Administration; Participant; Patients; Peptides; Pharmaceutical Preparations; Phase; Placebos; Prednisone; Prevention; Protocols documentation; Publications; Randomized; Rattus; Retinal; Safety; T-Lymphocyte; Testing; Therapeutic immunosuppression; Time; Toxic effect; United States National Institutes of Health; Uveitis; base; feeding; interstitial retinol-binding protein; oral tolerance; protein aminoacid sequence; treatment group; uveoretinitis

The effect of the oral administration of various antigens on the ocular immune response has been tested in the animal model for severe intraocular inflammatory disease, experimental autoimmune uveoretinitis (EAU), that is induced by both retinal S-antigen (S-Ag) and interphotoreceptor retinoid-binding protein (IRBP). Oral tolerance could be induced by repeatedly feeding S-Ag to rats. A randomized masked trial to evaluate the usefulness of S-Ag feeding in patients with intraocular inflammatory diseases finished recruitment in August 1995, with publication of the trial in early 1997. That study was aimed to evaluate the effect and safety of the oral administration of retinal antigens on various parameters of ocular inflammation. It was a phase I/II randomized, masked trial. In that study, patients with endogenous uveitis who were dependent on immunosuppressive agents were randomly assigned to receive either retinal S-antigen alone (n=10), retinal S-antigen and a mixture of soluble retinal antigens (n=10), retinal mixture of soluble antigens alone (n=10), or placebo (n-15). An attempt was then made to taper patients completely off their standard immunosuppressive therapy over an eight week period. Time to development of uveitis was the main study endpoint and was not statistically significantly different for any of the four treatment groups. However, the group receiving the purified S-Antigen alone appeared to be tapered off their immunosuppressive medication more successfully as compared to placebo (p=0.08), while all the other groups appeared to do worse than those receiving placebo. No toxic effects attributable to any treatment were observed. This study was used for further hypothesis development. Based on that and other studies. We have recently completed a study testing the use of Optiquel (provided under a CRADA by Enzo corporation) as a potential oral tolerance agent for uveitis. Optiquel is a B27PD peptide sequence found in several HLA-B antigens, most remarkably in all those that are associated with uveitis, such as B27, B51 and B44 (genetically linked to HLA A29). The objective of the ongoing masked randomized study was to evaluate the safety and efficacy of Optiquel as a corticosteroid-sparing agent for chronic non-infectious uveitis in participants receiving oral corticosteroid therapy alone or combined with an immunosuppressive agent in a proof-of-concept clinical trial. Eligible patients with non-infectious uveitis requiring at least 20 mg of oral prednisone to maintain a quiescent eye were eligible. The protocol was performed under IRB approval and an IND. It is also an NIH Center for Human Immunology approved study. The immunome is being extensively evaluated in collaboration with CHI. Using computational techniques to evaluate complex 15-color flow cytometric data, initial results suggest that alterations in B cells and T cells may be seen.

在动物模型中，已经对各种抗原的口服给药对眼部免疫反应的影响已在严重的眼内炎性疾病，实验性自身免疫性葡萄膜蛋白炎（EAU）中进行了测试，这是视网膜S-抗原（S-AG）诱导的。 可以通过反复将S-AG喂给大鼠来诱导口服耐受性。一项随机掩盖试验，以评估1995年8月在1997年8月招募的眼内炎症性疾病患者中S-AG喂养的有用性，并于1997年初发布了该试验。该研究的目的是评估视网膜抗原对眼球炎症各种参数的口服施用的影响和安全性。这是I/II期随机，掩盖试验。在该研究中，依赖免疫抑制剂的内源性葡萄膜炎的患者被随机分配单独接受视网膜S抗原（n = 10），视网膜S抗原和可溶性视网膜抗原的混合物（n = 10），单独使用可溶性抗原的视网膜混合物（n = 10）或位置（n = 10）或地位（n-15）。然后尝试在八周内完全逐渐减少其标准免疫抑制疗法的患者。葡萄膜炎发展的时间是主要研究终点，对于四个治疗组中的任何一个，在统计学上没有显着差异。但是，与安慰剂相比，仅接受纯化的S抗原的小组似乎更成功地从免疫抑制药物中逐渐减少了锥度（P = 0.08），而其他所有组似乎都比接受安慰剂的人更糟。未观察到任何归因于任何治疗的毒性作用。这项研究用于进一步的假设发展。基于该研究和其他研究。 我们最近完成了一项研究，该研究测试了使用Optiquel（由Enzo Corporation提供的Crada提供）作为葡萄膜炎的潜在口服耐受剂。 Optiquel是在几种HLA-B抗原中发现的B27PD肽序列，在所有与葡萄膜炎相关的HLA-B抗原中，例如B27，B51和B44（遗传上与HLA A29相关）。 正在进行的掩盖随机研究的目的是评估Optiquel作为慢性非感染性葡萄膜炎的皮质类固醇皮质固醇的安全性和功效，仅接受口服皮质类固醇治疗，或在一项证明的概念概念诊所临床试验中与免疫抑制剂结合使用。有资格的非感染葡萄膜炎患者需要至少20毫克的口服泼尼松以保持静止的眼睛。该协议是根据IRB批准和IND执行的。它也是NIH人类免疫学批准的研究中心。与CHI合作对免疫组进行了广泛的评估。使用计算技术评估复杂的15色流式细胞仪数据，最初的结果表明可以看到B细胞和T细胞的改变。