STUDIES OF NATURALLY OCCURING DEFECTS IN RESISTANCE TO INFECTION

这个子项目是利用由NIH/NCRR资助的中心拨款提供的资源的许多研究子项目之一。子项目和调查员(PI)可能从另一个NIH来源获得了主要资金，因此可能会出现在其他CRISE条目中。列出的机构是针对中心的，而不一定是针对调查员的机构。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，是测量对T细胞依赖的新抗原-噬菌体fX174的抗体反应，它可以评估抗原清除、初级IgM反应和决定扩增、类切换重组和体细胞超突变的次级反应。在大多数情况下，噬菌体的使用是诊断性的，很少进行研究。由于噬菌体是由FDA控制的，并且有IND编号，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，或者在某些情况下，需要进行骨髓移植(BMT)。骨髓移植成功后，fX174噬菌体免疫可用于确定骨髓受者的免疫系统是否已完全重建，以及进行标准的儿童免疫接种是否安全。为了评估对这种依赖T细胞的抗原的“成熟”免疫反应，每个患者首先进行一次注射，然后通过静脉途径用这种抗原进行强化注射(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2.5-5毫升血液)，并分析中和抗体含量。为了被选中进行噬菌体免疫，患者要么已知，要么怀疑有抗体缺陷。这种抗原对静脉注射免疫球蛋白的个体特别有用，因为如果个体接受免疫球蛋白注射，就不能使用召回抗原。我们的标准方案要求在免疫后一周、两周和四周采集血液样本进行抗体分析。

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 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.