DIABETES MELLITUS: IMMUNE RESPONSES TO INSULINS

糖尿病：胰岛素的免疫反应

• 批准号: 3153171
• 负责人: Philip Fireman
• 金额: $ 9.99万
• 依托单位: CHILDREN'S HOSP PITTSBURGH/UPMC HLTH SYS
• 依托单位国家: 美国
• 财政年份: 1984
• 资助国家: 美国
• 起止时间: 1984-07-01 至 1987-06-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/3153171
• 关键词: T lymphocyte; autoantibody; blood groups; enzyme linked immunosorbent assay; helper T lymphocyte; human population genetics; human subject; immune response genes; immunization; immunoglobulin E; immunoglobulin G; immunoglobulin M; immunoglobulin genes; influenza vaccines; insulin; leukocyte activation /transformation; leukocyte antigen typing; linkage mapping; major histocompatibility complex; pancreatic islets; suppressor T lymphocyte

Diabetes mellitus is a familial disease with a heterogeneous expression that includes immunologic as well as metabolic, renal, neurologic and vascular features. The long term objectives of our overall research program are to provide insights into the manifestations of this disease. The aims of this proposal are to delineate those immunologic and genetic components that may contribute to the pathogenesis of insulin-dependent diabetes mellitus (IDDM). The goals are to characterize prospectively the immune responses of patients with IDDM to human or pork insulins to ascertain if these immune responses are controlled by immune response (Ir) genes associated with or linked to the major histocompatibility complex (MHC) or other genetic markers. Besides measuring total insulin bound antibody, we will measure isotypic IgE, IgG and IgM antibodies to insulin along with lymphocyte proliferation responses to insulin. Those immune responses to insulin which may be detected at the time of diagnosis and before insulin treatment is instituted will be compared to the presence of islet cell antibodies. These immune responses will be compared to HLA-DR types, immunoglobulin allotypes (Gm and Km), Kidd blood and DNA restriction fragment length polymorphism. The possibility that there is impaired production of antibodies and cellular immune responses following immunization with influenza vaccine in patients with IDDM will be explored in a pilot study. Whether these immune responses to influenza vaccine in IDDM patients may be associated or linked to the MHC or other genetic markers will also be investigated. The subjects with IDDM to be studied will be recruited from the Pittsburgh IDDM Registry. This is one of the most extensive and complete registries of IDDM in the world with over 100 multiplex families with IDDM within the context of over 1,200 families evaluated. This well defined cohort of IDDM patients provide an exceptional opportunity to study prospectively the immunologic responses of these patients and their families as related to the development of IDDM.

糖尿病是一种具有异质性表现的家族性疾病 包括免疫学以及代谢、肾脏、神经和 血管特征。 我们整体研究的长期目标 计划旨在提供对该疾病表现的见解。 该提案的目的是描述那些免疫学和遗传学 可能导致胰岛素依赖型糖尿病发病机制的成分 糖尿病（IDDM）。 目标是前瞻性地描述 IDDM 患者对人或猪胰岛素的免疫反应 确定这些免疫反应是否受免疫反应 (Ir) 控制 与主要组织相容性复合体相关或相关的基因 (MHC) 或其他遗传标记。 除了测量总胰岛素结合 抗体，我们将测量胰岛素的同型 IgE、IgG 和 IgM 抗体 以及淋巴细胞对胰岛素的增殖反应。 那些免疫的人 对胰岛素的反应可以在诊断时检测到 在开始胰岛素治疗之前将与存在的情况进行比较 胰岛细胞抗体。 这些免疫反应将与 HLA-DR 进行比较 类型、免疫球蛋白同种异型（Gm 和 Km）、基德血和 DNA 限制 片段长度多态性。 存在受损的可能性 抗体的产生和细胞免疫反应 将探索 IDDM 患者流感疫苗的免疫接种 在一项试点研究中。 这些对流感疫苗的免疫反应是否 IDDM 患者可能与 MHC 或其他遗传相关或相关 标记也将被调查。 患有 IDDM 的研究对象 将从匹兹堡 IDDM 登记处招募。 这是其中之一 世界上最广泛、最完整的 IDDM 登记册，拥有 100 多个 超过 1,200 个家庭中包含 IDDM 的多重家庭 评价。 这个定义明确的 IDDM 患者队列提供了 前瞻性研究免疫反应的绝佳机会 这些患者及其家属认为与 IDDM 的发展有关。