HEPCIDIN AND THE ANEMIA OF CHRONIC DISEASE

这个子项目是利用由NIH/NCRR资助的中心拨款提供的资源的许多研究子项目之一。子项目和调查员(PI)可能从另一个NIH来源获得了主要资金，因此可能会出现在其他CRISE条目中。列出的机构是针对中心的，而不一定是针对调查员的机构。慢性病贫血的发病机制尚不清楚。新近发现的一种多肽--海普西丁，在糖原蓄积性疾病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Ia型糖原沉积病(GSDIa)患者铁的吸收和分布；(3)确定海普西丁作为慢性疾病贫血的介质在其他炎症条件下的作用。方法：在正常和病理状态下，包括GSDIa、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。由于糖原蓄积性疾病患者的肝腺瘤中已经显示出不适当的海普西丁表达，因此将在该人群中进行直接观察性研究，以使这些病变与红细胞生成和铁状态的指标之间有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。加深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失调的新疗法奠定基础

This subproject is one of many research subprojects utilizing the resources provided by a Center grant funded by NIH/NCRR. The subproject and investigator (PI) may have received primary funding from another NIH source, and thus could be represented in other CRISP entries. The institution listed is for the Center, which is not necessarily the institution for the investigator. 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 glycogen storage disease, 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 glycogen storage disease type Ia (GSDIa), and (3) 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 GSDIa, juvenile rheumatoid arthritis, and inflammatory bowel disease. As inappropriate hepcidin expression has been demonstrated in hepatic adenomas in patients with glycogen storage disease, 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