Structural Immunology

结构免疫学

基本信息

批准号：
8734176
负责人：
Leesa Deterding
金额：
$ 13.55万
依托单位：
NATIONAL INSTITUTE OF ENVIRONMENTAL HEALTH SCIENCES
依托单位国家：
美国
项目类别：
财政年份：
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/8734176
关键词：
Amino Acids Antibodies Antigens Antineutrophil Cytoplasmic Antibodies Architecture Autoantigens Autoimmune Diseases Autoimmune Process Autoimmunity Cells Chemicals Chronic Data Development Digestion Disease Elements Environmental Risk Factor Galactose Genes Genetic Genomics Goals Health Immunoglobulin Constant Region Immunoglobulin G Immunoglobulins Immunology Incidence Individual Inflammation Kidney Lacrimal gland structure Length Link Modification Molecular Oligosaccharides PRTN3 gene Pathogenesis Patients Pattern Plasma Polysaccharides Proteins Protocols documentation Role Salivary Glands Serum Sialic Acids Signal Transduction Sjogren&apos s Syndrome Structural Models Structure Surface Techniques Time glycosylation human disease liquid chromatography mass spectrometry protein function protein protein interaction protein structure structural biology three dimensional structure trend

项目摘要

Many autoimmune conditions are believed to result from chronic inflammation as a consequence of the interaction of genetic and environmental factors in susceptible individuals. One common feature in some autoimmune diseases is the decrease in terminal galactosylation of the constant region N-glycan of the total plasma immunoglobulin. The glycosylation pattern of the antibodies isolated from patients with ANCA-MPO (a kidney autoimmune disease) is being investigated to determine whether a similar trend is observed in individuals with other autoimmune disorders as we have seen before. A protocol for isolation of the antibody followed by SDS-PAGE, digestion, and LC/MS analyses is being developed. Structural and functional studies of the autoantigens are necessary to increase our understanding of the pathogenesis of Sjogrens syndrome. The function(s) of the primary autoantigen, LaSSB, associated with Sjogrens syndrome, a chronic rheumatic autoimmune disease that primarily targets the salivary and lacrimal glands, is unknown at this time, but the role of the LaSSB antigen is thought to be critical for understanding the mechanism of the development of autoimmunity. Structural and functional studies of this antigen are necessary to increase our understanding of the pathogenesis of Sjogrens syndrome. Structural studies involving chemical modification, oxidative footprinting, and H/D exchange in combination with mass spectrometric analyses have been used to gain information regarding the surface accessibility of amino acids in LaSSB. Collectively, these data provide useful information regarding the tertiary structures of LaSSB and has been used to help generate a structural model of the full-length LaSSB. The glycosylation pattern of antibodies and antigens isolated from patients with ANCA-MPO and ANCA-PR3 (kidney autoimmune diseases) are being investigated. In PR3-ANCA disease, N-linked oligosaccharides deficient in terminal sialic acid and galactose (IgG-G0 glycan form) is significantly increased and the high incidence of IgG-G0 in serum correlates with disease activity. ANCA-MPO sera is investigated to determine whether there is a similar pattern of abnormal IgG glycosylation observed and whether that correlates with disease activity.

许多自身免疫性疾病被认为是由易感个体遗传和环境因素相互作用导致的慢性炎症引起的。一些自身免疫性疾病的一个共同特征是总血浆免疫球蛋白恒定区 N-聚糖的末端半乳糖基化减少。正在研究从 ANCA-MPO（一种肾脏自身免疫性疾病）患者中分离出的抗体的糖基化模式，以确定是否在患有其他自身免疫性疾病的个体中观察到类似的趋势，正如我们之前所看到的。正在开发用于分离抗体，然后进行 SDS-PAGE、消化和 LC/MS 分析的方案。自身抗原的结构和功能研究对于增加我们对干燥综合征发病机制的了解是必要的。与干燥综合征（一种主要针对唾液腺和泪腺的慢性风湿性自身免疫性疾病）相关的主要自身抗原 LaSSB 的功能目前尚不清楚，但 LaSSB 抗原的作用被认为对于干燥综合征至关重要。了解自身免疫发展的机制。该抗原的结构和功能研究对于增加我们对干燥综合征发病机制的了解是必要的。涉及化学修饰、氧化足迹和 H/D 交换的结构研究与质谱分析相结合，已用于获取有关 LaSSB 中氨基酸表面可及性的信息。总的来说，这些数据提供了有关 LaSSB 三级结构的有用信息，并已用于帮助生成全长 LaSSB 的结构模型。正在研究从 ANCA-MPO 和 ANCA-PR3（肾脏自身免疫性疾病）患者分离的抗体和抗原的糖基化模式。在 PR3-ANCA 疾病中，末端唾液酸和半乳糖缺陷的 N 连接寡糖（IgG-G0 聚糖形式）显着增加，血清中 IgG-G0 的高发生率与疾病活动性相关。研究 ANCA-MPO 血清以确定是否观察到类似的异常 IgG 糖基化模式以及这是否与疾病活动相关。