Structural Immunology

结构免疫学

• 批准号: 8929816
• 负责人: Leesa Deterding
• 金额: $ 17.09万
• 依托单位: NATIONAL INSTITUTE OF ENVIRONMENTAL HEALTH SCIENCES
• 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/8929816
• 关键词: Amino Acids; Antibodies; Antigens; Antineutrophil Cytoplasmic Antibodies; Architecture; Autoantigens; Autoimmune Diseases; Autoimmune Process; Autoimmunity; Cells; Chemicals; Chronic; Data; Development; Disease; Elements; Environmental Risk Factor; Galactose; Genes; Genetic; Genomics; Goals; Health; Immunoglobulin G; Immunoglobulins; Immunology; Incidence; Individual; Inflammation; Kidney; Lacrimal gland structure; Length; Link; Modification; Molecular; Oligosaccharides; PRTN3 gene; Pathogenesis; Patients; Pattern; Plasma; Polysaccharides; Proteins; Role; Salivary Glands; Serum; Sialic Acids; Signal Transduction; Sjogren' s Syndrome; Structural Models; Structure; Surface; Techniques; Time; glycosylation; human disease; protein function; protein protein interaction; protein structure; structural biology; three dimensional structure; trend

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 a change in the glycan pattern of plasma immunoglobulins. 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. The glycosylation pattern of antigens isolated from patients with ANCA-MPO and ANCA-PR3 (kidney autoimmune diseases) are also 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. Structural and functional studies of the antigens of autoimmune diseases are necessary to increase our understanding of the pathogenesis of the disease. 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.

人们认为，许多自身免疫性疾病是由于易感人群中遗传和环境因素的相互作用而导致的。某些自身免疫性疾病中的一个常见特征是血浆免疫球蛋白的聚糖模式的变化。正在研究从ANCA-MPO患者（一种肾脏自身免疫性疾病）中分离出的抗体的糖基化模式，以确定在患有其他自身免疫性疾病的患者中是否像以前看到的那样观察到类似的趋势。 还研究了从ANCA-MPO和ANCA-PR3患者（肾脏自身免疫性疾病）中分离出的抗原的糖基化模式。 在Pr3- anca疾病中，N连接的寡糖缺乏末端唾液酸和半乳糖（IgG-G0聚糖形式）显着增加，并且血清中IgG-G0的高发病率与疾病活性相关。 研究了ANCA-MPO血清，以确定是否观察到IgG糖基化异常的模式以及是否与疾病活性相关。 自身免疫性疾病抗原的结构和功能研究对于增加我们对疾病发病机理的理解是必要的。与Sjogrens综合征相关的原发性自身抗原LASSB的功能是一种慢性风湿性自身免疫性疾病，主要针对唾液和泪腺，但目前尚不清楚。该抗原的结构和功能研究对于增加我们对Sjogrens综合征发病机理的理解是必要的。 涉及化学修饰，氧化足迹和H/D交换与质谱分析的结构研究已用于获取有关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。