Complement deficiency and environment in autoimmunity

自身免疫中的补体缺乏和环境

• 批准号: 7338302
• 负责人: MATILDA W NICHOLAS
• 金额: $ 2.8万
• 依托单位: UNIV OF NORTH CAROLINA CHAPEL HILL
• 依托单位国家: 美国
• 财政年份: 2006
• 资助国家: 美国
• 起止时间: 2006-01-01 至 2009-05-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/7338302
• 关键词: Affinity; Antibodies; Antigens; Apoptosis; Apoptotic; Autoantibodies; Autoimmune Diseases; Autoimmunity; B-Cell Development; B-Lymphocyte Subsets; B-Lymphocytes; Bulla; Cells; Complement; Complement 3d Receptors; Complement Receptor; Data; Development; Disease; Dose; Environment; Environmental Exposure; Enzyme-Linked Immunosorbent Assay; Etiology; Flow Cytometry; Generations; Genetic; Heavy-Chain Immunoglobulins; Human; Injection of therapeutic agent; Link; Lupus Erythematosus; Membrane; Mercury; Modeling; Mus; Nuclear; Nuclear Protein; Nuclear Proteins; Patients; Pb clearance; Peripheral; Population; Production; Reactive Oxygen Species; Regulation; Relapse; Role; Self Tolerance; Silicon Dioxide; Sm antigen; Surface; System; Systemic Lupus Erythematosus; Testing; To autoantigen; Transgenic Organisms; Ultraviolet Rays; Virus; Work; autoreactive B cell; complement deficiency; environmental stressor; irradiation; ultraviolet irradiation

DESCRIPTION (provided by applicant): Systemic lupus erythematosus (SLE) is a devastating autoimmune disease marked by the production of autoantibodies, anti-Smith (Sm) being the most specific for the disease. The etiology of SLE is known to have significant genetic and environmental components. Abundant data link deficiencies of the complement system to the development of autoimmune diseases, particularly SLE. Deficiencies of either complement protein C4 or the complement receptor CR2 (CD21) trigger development of SLE-like disease in mice. Partial or complete C4 deficiency strongly predisposes to SLE in humans, and recently, decreased CD21 expression has been observed in human SLE patients. How these genetic deficiencies in complement interact with environmental effectors to trigger disease is unknown. We have crossed mice deficient for C4 or CD21 to a transgenic line which expresses an Ig heavy-chain specific for Sm. We propose to study the effect of environmental stressors on anti-Sm B cells and the development of anti-Sm antibodies in these mice to elucidate the interplay between genetic and environmental components of SLE development.

描述（由申请人提供）：系统性红斑狼疮（SLE）是一种毁灭性的自身免疫性疾病，其特征是产生自身抗体，抗Smith（Sm）是该疾病最特异的抗体。SLE的病因学已知具有显著的遗传和环境成分。丰富的数据链接补体系统的缺陷发展的自身免疫性疾病，特别是系统性红斑狼疮。补体蛋白C4或补体受体CR2（CD21）的缺陷引发小鼠SLE样疾病的发展。部分或完全C4缺乏强烈地倾向于SLE在人类中，最近，减少的CD21表达已被观察到在人类SLE患者。这些补体的遗传缺陷如何与环境效应物相互作用以引发疾病尚不清楚。我们将C4或CD 21缺陷小鼠与表达Sm特异性IG重链的转基因系杂交。我们建议研究环境应激对抗Sm B细胞和抗Sm抗体在这些小鼠中的发展的影响，以阐明SLE发展的遗传和环境成分之间的相互作用。