Disturbed iron metabolism in erythropoietic protoporphyria and association of GDF15 and gender with disease severity
Disturbed iron metabolism in erythropoietic protoporphyria and association of GDF15 and gender with disease severity
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DOI：
10.1007/s10545-017-0017-7
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发表时间：
2017-05-01
影响因子：
4.2
通讯作者：
Biolcati, Gianfranco
中科院分区：
文献类型：
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作者：
Barman-Aksoezen, Jasmin;Girelli, Domenico;Biolcati, Gianfranco
红细胞生成性原卟啉症 (EPP) 患者的铁螯合酶活性降低，该酶催化铁插入原卟啉 IX (PPIX) 形成血红素。由于亚铁螯合酶缺乏，PPIX 会积累并导致严重的光敏性。在不同的患者中，PPIX的浓度差异很大。除了光敏性外，患者还经常表现出低血清铁和小细胞低色素性贫血。本研究的目的是 (1) 寻找与 EPP 中 PPIX 浓度相关的因素，以及 (2) 描述 EPP 贫血的特征，即是否是绝对铁缺乏或慢性病贫血 (ACD) 的结果。对 67 名 EPP 患者（51 名意大利人和 16 名瑞士人）和 21 名健康志愿者的血液样本进行了分析。与对照组相比，EPP 患者的铁蛋白 (p = 0.021) 和铁调素 (p = 0.031) 浓度较低，锌原卟啉 (p < 0.0001) 和可溶性转铁蛋白受体 (p = 0.0007) 浓度较高。这表明EPP的贫血是由绝对缺铁引起的。在 EPP 患者中，PPIX 浓度与生长分化因子 (GDF) 15 (p = 0.012) 和男性性别 (p = 0.015) 相关。在铁充足的患者亚组中，血红蛋白水平正常，这表明铁而非亚铁螯合酶是 EPP 患者血红素合成的限制因素。
Patients with erythropoietic protoporphyria (EPP) have reduced activity of the enzyme ferrochelatase that catalyzes the insertion of iron into protoporphyrin IX (PPIX) to form heme. As the result of ferrochelatase deficiency, PPIX accumulates and causes severe photosensitivity. Among different patients, the concentration of PPIX varies considerably. In addition to photosensitivity, patients frequently exhibit low serum iron and a microcytic hypochromic anemia. The aims of this study were to (1) search for factors related to PPIX concentration in EPP, and (2) characterize anemia in EPP, i.e., whether it is the result of an absolute iron deficiency or the anemia of chronic disease (ACD). Blood samples from 67 EPP patients (51 Italian and 16 Swiss) and 21 healthy volunteers were analyzed. EPP patients had lower ferritin (p = 0.021) and hepcidin (p = 0.031) concentrations and higher zinc-protoporphyrin (p < 0.0001) and soluble-transferrin-receptor (p = 0.0007) concentrations compared with controls. This indicated that anemia in EPP resulted from an absolute iron deficiency. Among EPP patients, PPIX concentrations correlated with both growth differentiation factor (GDF) 15 (p = 0.012) and male gender (p = 0.015). Among a subgroup of patients who were iron replete, hemoglobin levels were normal, which suggested that iron but not ferrochelatase is the limiting factor in heme synthesis of individuals with EPP.