STUDIES OF NATURALLY OCCURING DEFECTS IN RESISTANCE TO INFECTION

天然存在的抗感染缺陷的研究

• 批准号: 7379300
• 负责人: HANS D OCHS
• 金额: $ 0.15万
• 依托单位: UNIVERSITY OF WASHINGTON
• 依托单位国家: 美国
• 财政年份: 2006
• 资助国家: 美国
• 起止时间: 2006-04-01 至 2007-03-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/7379300
• 关键词: STUDIES; NATURALLY; OCCURING; DEFECTS; RESISTANCE

This subproject is one of many research subprojects utilizing the resources provided by a Center grant funded by NIH/NCRR. The subproject and investigator (PI) may have received primary funding from another NIH source, and thus could be represented in other CRISP entries. The institution listed is for the Center, which is not necessarily the institution for the investigator. The purpose of this ongoing study is to evaluate the immune status of patients with primary immunodeficiency disorders. One aspect of this investigation, and the only subject of this application, is to measure the antibody responses to the T cell-dependent neoantigen, Bacteriophage fX174, which allows assessment of antigen clearance, the primary IgM response and the secondary response that determines amplification, class switch recombination and somatic hypermutation. Use of Bacteriophage is, in most instances, diagnostic and very rarely research. Since Bacteriophage is controlled by the FDA and has an IND number, we need to obtain consent from all patients independent of its use as a diagnostic tool or as a research tool. The response to Bacteriophage will help us to determine the need for immunoglobulin therapy or, in some cases, for bone marrow transplantation (BMT). Following successful BMT, Bacteriophage fX174 immunization may be used to determine if the marrow recipient's immune system has been fully reconstituted and if it is safe to give standard childhood immunizations. To assess a "mature" immune response to this T cell-dependent antigen, each patient is immunized with a primary injection followed by booster injections (up to three or four times) with this antigen by the intravenous route. The standard dose is 0.02ml/kg body weight. Samples (usually 2.5 - 5ml of blood) are drawn before and after the phage immunization and analyzed for neutralizing antibody content. In order to be selected for immunization with Bacteriophage, patients are either known or suspected to have an antibody deficiency. This antigen is especially useful in individuals on IVIG because recall antigens cannot be used if an individual receives immunoglobulin infusions. Our standard protocol requests that samples of blood are obtained for antibody analysis at one, two and four weeks post immunization.

本子项目是利用由NIH/NCRR资助的中心赠款提供的资源的众多研究子项目之一。子项目和研究者（PI）可能已经从另一个NIH来源获得了主要资金，因此可以在其他CRISP条目中表示。列出的机构是中心的，不一定是研究者的机构。这项正在进行的研究的目的是评估原发性免疫缺陷疾病患者的免疫状态。这项研究的一个方面，也是这项应用的唯一主题，是测量抗体对T细胞依赖性新抗原，噬菌体fX174的反应，它允许评估抗原清除，主要的IgM反应和决定扩增，类开关重组和体细胞超突变的次要反应。在大多数情况下，噬菌体的使用是诊断性的，很少用于研究。由于噬菌体是由FDA控制的，并且有一个IND号，我们需要获得所有患者的同意，而不是将其用作诊断工具或研究工具。对噬菌体的反应将帮助我们确定是否需要免疫球蛋白治疗，在某些情况下，是否需要骨髓移植（BMT）。在骨髓移植成功后，噬菌体fX174免疫可用于确定骨髓受体的免疫系统是否已完全重建，以及给予标准儿童免疫是否安全。为了评估对这种T细胞依赖性抗原的“成熟”免疫反应，每个患者通过静脉途径对这种抗原进行初次注射，然后进行加强注射（最多三到四次）。标准剂量为0.02ml/kg体重。在噬菌体免疫前后抽取样本（通常为2.5 - 5ml血液），分析中和抗体含量。为了选择进行噬菌体免疫接种，患者要么已知，要么怀疑有抗体缺乏。这种抗原在接受免疫球蛋白输注的个体中特别有用，因为如果个体接受免疫球蛋白输注，则不能使用召回抗原。我们的标准方案要求在免疫后1周、2周和4周采集血液样本进行抗体分析。