STUDIES OF NATURALLY OCCURRING DEFECTS IN RESISTANCE TO INFECTION

这个子项目是许多利用 由NIH/NCRR资助的中心赠款提供的资源。子项目和 研究者（PI）可能从另一个NIH来源获得了主要资金， 因此可以在其他CRISP条目中表示。所列机构为 研究中心，而研究中心不一定是研究者所在的机构。 这项正在进行的研究的目的是评价原发性免疫缺陷疾病患者的免疫状态。 本研究的一个方面和本申请的唯一主题是测量对T细胞依赖性新抗原噬菌体phiX 174的抗体应答，其允许评估抗原清除、初级IgM应答和决定扩增、类别转换重组和体细胞超变的次级应答。 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，并有一个IND编号，我们需要获得所有患者的同意，独立于其作为诊断工具或作为研究工具的使用。 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，或者在某些情况下，是否需要骨髓移植（BMT）。 在成功的BMT之后，噬菌体phiX 174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接种是否安全。 为了评估对该T细胞依赖性抗原的“成熟”免疫应答，通过静脉内途径用该抗原初次注射随后加强注射（最多三或四次）来免疫每个患者。 这种抗原在接受IVIG的个体中特别有用，因为如果个体接受免疫球蛋白输注，则不能使用回忆抗原。 我们的标准方案要求在免疫后1周、2周和4周获得血液样品用于抗体分析。

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 phiX174, 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 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 phiX174 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. 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.