Hepcidin Expression in the Anemia of Chronic Disease

描述（由申请人提供）： 慢性病贫血的发病机制尚不清楚。 最近鉴定的肽，hepcidin，已被发现在GSD（GSD）的肝腺瘤中异常表达，导致类似于慢性疾病贫血中所见的耐铁性缺铁性贫血。 铁调素被假定参与慢性疾病贫血的发病机制，这些研究旨在表征铁调素在正常铁稳态和慢性疾病贫血受试者中的作用。 具体目的如下：1）评估腺瘤肿瘤负荷与贫血之间的关系; 2）表征正常对照、贫血患者和GSD 1型患者在24小时内的铁吸收和分布。（GSD 1a; 3）比较正常人和GSD 1a患者的铁调素表达，以及4）确定铁调素作为慢性疾病贫血的介质在具有其他炎性病症的患者中的作用。 方法学：铁稳态和hepcidin表达之间的关系将在正常和病理状态，包括GSD 1a，幼年类风湿性关节炎，炎症性肠病进行研究。 由于在GSD患者的肝腺瘤中已经证明了不适当的铁调素表达，因此将在该人群中进行直接观察性研究，以进一步研究这些病变与红细胞生成和铁状态指数之间的临床相关性。 将在所有受试者中研究铁的口服吸收，以确定铁调素与铁吸收之间的关系。 对于炎性疾病，将在疾病缓解和加重期间进行口服铁激发试验和铁调素的直接测量。 铁调素和炎症标志物之间的关系也将被调查。 通过这些研究，铁调素作为慢性疾病贫血介质的作用将得到阐明。 对慢性疾病贫血的病理生理学的进一步了解将为贫血和铁稳态紊乱的新治疗奠定基础。

DESCRIPTION (provided by applicant): The pathogenesis of the anemia of chronic disease is not understood. A recently identified peptide, hepcidin, has been found to be aberrantly expressed in hepatic adenomas in GSD (GSD), resulting in an iron-resistant iron-deficiency anemia similar to that seen in the anemia of chronic disease. Hepcidin is postulated to be involved in the pathogenesis of the anemia of chronic disease, and these investigations are aimed at characterizing the role of hepcidin in both normal iron homeostasis and in subjects with the anemia of chronic disease. The specific aims are the following: 1) To evaluate the relationship between adenoma tumor burden and anemia; 2) To characterize iron absorption and distribution in normal controls, anemic patients, and patients with GSD Type 1 at (GSD1a; 3) To compare hepcidin expression in normal individuals and patients with GSD1a, and 4) To determine the role of hepcidin as a mediator of the anemia of chronic disease in patients with other inflammatory conditions. Methodology: The relationship between iron homeostasis and hepcidin expression will be studied in normal and pathologic states including GSD1a, juvenile rheumatoid arthritis, and inflammatory bowel disease. As inappropriate hepcidin expression has been demonstrated in hepatic adenomas in patients with GSD, direct observational studies in this population will be performed to allow further clinical correlation between these lesions and indices of erythropoiesis and iron status. Oral absorption of iron will be investigated in all subjects to define the relationship between hepcidin and iron absorption. For the inflammatory disorders, the oral iron challenge tests and direct measurement of hepcidin will be performed during periods of disease remission and exacerbation. The relationship between hepcidin and inflammatory markers will also be investigated. Through these studies, the role of hepcidin as a mediator of anemia of chronic disease will be elucidated. Improved understanding of the pathophysiology of the anemia of chronic disease will lay the foundation for new treatments for anemia and disorders of iron homeostasis.