Structural Immunology

结构免疫学

• 批准号: 9550175
• 负责人: Leesa Deterding
• 金额: $ 5.52万
• 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/9550175
• 关键词: Amino Acids; Antibodies; Antigens; Antineutrophil Cytoplasmic Antibodies; Architecture; Autoantigens; Autoimmune Diseases; Autoimmune Process; Autoimmunity; Cell Communication; Chemicals; Chronic; Data; Development; Disease; Disease remission; Elements; Environmental Risk Factor; Exhibits; Galactose; Genes; Genetic; Genomics; Goals; Health; Immunoglobulin G; Immunoglobulins; Immunology; Individual; Inflammation; Kidney; Lacrimal gland structure; Length; Modification; Molecular; PRTN3 gene; Pathogenesis; Patients; Pattern; Plasma; Polysaccharides; Proteins; Role; Salivary Glands; 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 levels of digalactosylated structures and terminally sialylated glycoforms on the Fc portion of total IgG from active PR3-ANCA patient significantly increased during disease remission and regained glycosylation levels indiscernible from those in healthy controls. In contrast, Fc N-glycan levels of total IgG from MPO-ANCA patients did not correlate with disease activity. Notably, MPO-ANCA patients continued to exhibit a deficit of terminal sialic acid and galactose residues during disease remission and, therefore, Fc N-glycan levels never appeared similar to healthy controls. 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。 在疾病缓解期间，活性PR3-ANCA患者的FC总IgG的FC部分的二甲基乳糖基化结构和终末糖化糖型的水平显着增加，并从健康对照中恢复不可见力的糖基化水平。 相反，来自MPO-ANCA患者的总IgG的FC N-聚糖水平与疾病活性无关。 值得注意的是，MPO-ANCA患者在疾病缓解过程中继续表现出终末唾液酸和半乳糖残基的不足，因此，FC N-聚糖水平从未像健康对照相似。 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。