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。最近发现的一种多肽，海普西丁，在GSD(GSD)的肝腺瘤中异常表达，导致一种类似于慢性病贫血的铁抵抗缺铁性贫血。海普西丁被认为与慢性病贫血的发病机制有关，这些研究旨在确定海普西丁在正常铁稳态和慢性病贫血患者中的作用。 其具体目的如下：1)评价腺瘤肿瘤负荷与贫血的关系；2)研究正常对照组、贫血患者和GSD1a 1型GSD患者中铁的吸收和分布特征；3)比较正常人和GSD1a患者中Hepsidin的表达；4)确定在有其他炎症性疾病的患者中，Hepsidin在慢性病贫血中的中介作用。 方法：在正常和病理状态下，包括GSD1a、幼年类风湿性关节炎和炎症性肠病，研究铁稳态和海普西丁表达之间的关系。由于在GSD患者的肝腺瘤中显示出不适当的海普西丁表达，将在这一人群中进行直接的观察性研究，以允许这些病变与红细胞生成和铁状态的指标之间进一步的临床相关性。将对所有受试者的口服铁吸收进行调查，以确定海普西丁和铁吸收之间的关系。对于炎症性疾病，在疾病缓解和恶化期间，将进行口服铁激发试验和直接测定海普西丁。此外，还将研究海普西丁与炎症标志物的关系。通过这些研究，将阐明海普西丁作为慢性病贫血的介体的作用。提高对慢性病贫血的病理生理学的认识，将为治疗贫血和铁稳态紊乱的新疗法奠定基础。

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.