Department of Hematology, General Hospital of Tianjin Medical University, Tianjin, China.
Third Medical Center of Chinese People's Liberation Army General Hospital, Beijing, China.
Ann Med. 2023 Dec;55(1):231-240. doi: 10.1080/07853890.2022.2157475.
Autoimmune hemolytic anemia (AIHA) is rare heterogeneous disorder characterized by red blood cell (RBC) destruction via auto-antibodies, and after RBC is destroyed, proinflammatory danger-associated molecular patterns including extracellular hemoglobin, heme, and iron which causing cell injury. And oxidative stress represents one of the most significant effects of chronic hemolysis. can improve the symptoms of anemia patients with kidney disease and tumors and are beneficial in promoting recovery from chronic inflammation. Therefore, it is presumed that can improve the symptoms of AIHA. We aimed to investigate iron metabolism in AIHA and effects of on AIHA murine model.
Nineteen hemolytic episode AIHA patients, 10 remission patients and 10 healthy controls (HCs) were enrolled in this study. Serum hepcidin, ferritin and other related indicators of iron metabolism were measured. Mouse models of AIHA were established and received high, medium, or low doses of by gavage daily for 14 and 28 days respectively. The level of RBCs, Hb, bilirubin, LDH, hepcidin, and the expression level of hepcidin mRNA, and hepatic ferroportin 1(FPN1) protein were evaluated.
Serum hepcidin in hemolytic episode AIHA patients and remission patients were significantly higher than that in HCs ( 0.0083 and = 0.0473, respectively). Serum ferritin in hemolytic AIHA patients was significantly higher than that in HCs ( 0.008). Serum transferrin saturation levels are increased in patients with AIHA[ (57.21 ± 8.96) %]. EPO in hemolytic group was higher than that in healthy control (＜0.05). In AIHA mouse models, IBIL decreased after 14 days of high dose drug intervention. After 28 days, TBIL and IBIL both significantly decreased in all dose groups and LDH significantly decreased in the medium-and high-dose groups. Body weight improved, and the level of RBCs, Hb and hepcidin in the high-dose group returned to normal. After 14 and 28 days of intervention, hepatic hepcidin mRNA in all dose group significantly decreased. Hepatic FPN1 protein which were significantly lower in the AIHA mouse models, increased in all dose groups after drug intervention for 28 days.
Iron metabolism abnormalities exists in AIHA patients and can ameliorate hemolysis and improve iron metabolism in AIHA mouse models.KEY MESSAGESIron metabolism abnormalities exists in hemolytic episode AIHA patients. Hepcidin and ferritin levels significantly elevated and also correlated with the severity of AIHA patients. can ameliorate hemolysis and prompt the recovery of AIHA.
自身免疫性溶血性贫血（AIHA）是一种罕见的异质性疾病，其特征是红细胞（RBC）通过自身抗体破坏，并且在 RBC 被破坏后，促炎危险相关分子模式包括细胞外血红蛋白、血红素和铁，这些物质会导致细胞损伤。氧化应激是慢性溶血的最显著影响之一。可以改善肾病和肿瘤患者贫血的症状，并有利于促进慢性炎症的恢复。因此，推测可以改善 AIHA 的症状。我们旨在研究 AIHA 中的铁代谢以及对 AIHA 小鼠模型的影响。
本研究纳入了 19 名溶血性发作 AIHA 患者、10 名缓解患者和 10 名健康对照者（HCs）。测量了血清铁调素、铁蛋白和其他铁代谢相关指标。建立了 AIHA 小鼠模型，并通过灌胃分别给予高、中、低剂量的 14 和 28 天。评估了 RBC 水平、Hb、胆红素、LDH、铁调素和铁调素 mRNA 的表达水平以及肝铁蛋白 1（FPN1）蛋白。
溶血性发作 AIHA 患者和缓解患者的血清铁调素明显高于 HCs（分别为 0.0083 和 0.0473）。溶血性 AIHA 患者的血清铁蛋白明显高于 HCs（0.008）。AIHA 患者的血清转铁蛋白饱和度升高[（57.21±8.96）%]。溶血组的 EPO 高于健康对照组（＜0.05）。在 AIHA 小鼠模型中，高剂量药物干预 14 天后 IBIL 降低。28 天后，所有剂量组的 TBIL 和 IBIL 均显著降低，中、高剂量组的 LDH 显著降低。体重改善，高剂量组 RBC 水平、Hb 和铁调素恢复正常。干预 14 和 28 天后，所有剂量组的肝铁调素 mRNA 均显著降低。肝 FPN1 蛋白在 AIHA 小鼠模型中明显降低，药物干预 28 天后所有剂量组均增加。
AIHA 患者存在铁代谢异常，而能改善溶血并改善 AIHA 小鼠模型中的铁代谢。
溶血性发作 AIHA 患者存在铁代谢异常。铁调素和铁蛋白水平显著升高，并与 AIHA 患者的严重程度相关。可以改善溶血并促使 AIHA 恢复。
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