DIABETES MELLITUS: IMMUNE RESPONSES TO INSULINS

糖尿病是一种家族性疾病， 这包括免疫以及代谢，肾脏，神经和 血管特征 我们整体研究的长远目标 该计划旨在深入了解这种疾病的表现。 这项建议的目的是描绘那些免疫和遗传 可能有助于胰岛素依赖性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胰岛素或猪胰岛素的免疫应答 确定这些免疫应答是否受免疫应答（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 抗体，我们将测量胰岛素的同种型IgE、IgG和IgM抗体 沿着淋巴细胞对胰岛素的增殖反应。 那些免疫 在诊断时可检测到的胰岛素反应， 在胰岛素治疗开始之前，将与 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）、Kidd血型和DNA限制 片段长度多态性 有可能是受损的 产生抗体和细胞免疫应答 将探索胰岛素依赖型糖尿病患者的流感疫苗免疫接种 in a pilot试点study研究. 是否这些免疫反应对流感疫苗在 胰岛素依赖型糖尿病患者可能与MHC或其他遗传因素相关或相关。 标记也将被调查。 待研究的IDDM受试者 将从匹兹堡胰岛素依赖型糖尿病登记处招募。 这是其中一 世界上最广泛和最完整的IDDM登记处， 在超过1，200个家庭的背景下， 评估。 这一明确定义的IDDM患者队列提供了一个 这是一个前瞻性研究免疫反应的绝佳机会， 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.