DIABETES MELLITUS: IMMUNE RESPONSES TO INSULINS

糖尿病是一种表现异质性的家族性疾病。 包括免疫学以及新陈代谢、肾脏、神经学和 血管特征。我们整体研究的长期目标 计划是提供对这种疾病的表现的洞察力。 这项提案的目的是描绘出那些免疫学和遗传学 可能参与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 胰岛素依赖型糖尿病患者对人或猪肉胰岛素的免疫应答 确定这些免疫反应是否由免疫反应(Ir)控制 与主要组织相容性复合体相关或连锁的基因 (MHC)或其他遗传标记。除了测量总胰岛素结合量 抗体，我们将检测胰岛素的同型IgE、Ig G和Ig M抗体 以及对胰岛素的淋巴细胞增殖反应。那些免疫的 对胰岛素的反应，可在诊断时检测到 在开始胰岛素治疗之前，将其比作 胰岛细胞抗体。这些免疫反应将与人类白细胞抗原DR进行比较 类型、免疫球蛋白同种异型(GM和KM)、KIDD血和DNA限制 片段长度多态。有一种可能性被削弱了 抗体的产生和细胞免疫反应 将探索在IDDM患者中接种流感疫苗 在一项初步研究中。这些对流感疫苗的免疫反应是否在 IDDM患者可能与MHC或其他基因相关或连锁 记分员也将被调查。IDDM有待研究的对象 将从匹兹堡IDDM登记处招聘。这是世界上 世界上最广泛和最完整的IDDM登记，超过100 在1200多个家庭中患有IDDM的多个家庭 已评估。这一定义明确的IDDM患者队列提供了 前瞻研究人类免疫应答的难得机会 这些患者及其家属与IDDM的发生有关。

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.