Xanthine oxidase levels and immune dysregulation are independently associated with anemia in Plasmodium falciparum malaria.
Xanthine oxidase levels and immune dysregulation are independently associated with anemia in Plasmodium falciparum malaria.
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DOI：
10.1038/s41598-023-41764-4
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发表时间：
2023-09-07
影响因子：
4.6
通讯作者：
中科院分区：
文献类型：
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严重贫血是导致严重疟疾儿童死亡的一个重要因素。疟疾中的贫血是一种多因素并发症，因为红细胞生成障碍、溶血和未感染红细胞（RBC）的吞噬清除可促成该综合征。高水平的氧化应激和免疫失调被认为是导致严重疟疾性贫血的原因，促进了未感染红细胞的清除。在一组552名患有严重疟疾的乌干达儿童中，我们测量了黄嘌呤氧化酶（XO）的水平，这是一种在疟疾患者血浆中升高的氧化酶。严重贫血儿童的XO水平明显高于未患严重贫血的严重疟疾儿童。XO水平与RBC血红蛋白呈负相关（ρ =-0.25，p < 0.0001），表明这种酶与严重贫血之间存在关系。当与免疫复合物和磷脂酰丝氨酸自身免疫抗体的水平相比，以前与疟疾患者严重贫血的因素，我们观察到，XO是不相关的，这表明XO是通过一个独立的机制与严重贫血。XO与虚脱、酸中毒、黄疸、呼吸窘迫和肾损伤相关，这可能反映了这种酶与严重疟疾病理学的更广泛关系。由于XO的抑制剂是已经批准用于人类的廉价且耐受性良好的药物，因此XO作为严重疟疾贫血和其他疟疾并发症的贡献者的验证可能为急需的疟疾预防治疗开辟新的可能性。
Severe anemia is an important contributor to mortality in children with severe malaria. Anemia in malaria is a multi-factorial complication, since dyserythropoiesis, hemolysis and phagocytic clearance of uninfected red blood cells (RBCs) can contribute to this syndrome. High levels of oxidative stress and immune dysregulation have been proposed to contribute to severe malarial anemia, facilitating the clearance of uninfected RBCs. In a cohort of 552 Ugandan children with severe malaria, we measured the levels of xanthine oxidase (XO), an oxidative enzyme that is elevated in the plasma of malaria patients. The levels of XO in children with severe anemia were significantly higher compared to children with severe malaria not suffering from severe anemia. Levels of XO were inversely associated with RBC hemoglobin (ρ = − 0.25, p < 0.0001), indicating a relation between this enzyme and severe anemia. When compared with the levels of immune complexes and of autoimmune antibodies to phosphatidylserine, factors previously associated with severe anemia in malaria patients, we observed that XO is not associated with them, suggesting that XO is associated with severe anemia through an independent mechanism. XO was associated with prostration, acidosis, jaundice, respiratory distress, and kidney injury, which may reflect a broader relation of this enzyme with severe malaria pathology. Since inhibitors of XO are inexpensive and well-tolerated drugs already approved for use in humans, the validation of XO as a contributor to severe malarial anemia and other malaria complications may open new possibilities for much needed adjunctive therapy in malaria.
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DOI：
10.1182/asheducation-2009.1.87
发表时间：
2009
期刊：
Hematology. American Society of Hematology. Education Program
影响因子：
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作者：
Haldar K;Mohandas N
通讯作者：
Mohandas N
DOI：
10.4049/jimmunol.1103812
发表时间：
2013-04-01
期刊：
Journal of immunology (Baltimore, Md. : 1950)
影响因子：
--
作者：
Fernandez-Arias C;Lopez JP;Hernandez-Perez JN;Bautista-Ojeda MD;Branch O;Rodriguez A
通讯作者：
Rodriguez A
影响因子：
20.3
作者：
Liu, Yunfeng;Pal, Mouli;Yazdanbakhsh, Karina
通讯作者：
Yazdanbakhsh, Karina
DOI：
10.4269/ajtmh.2005.72.593
发表时间：
2005-05-01
影响因子：
3.3
作者：
Mibei, EK;Orago, ASS;Stoute, JA
通讯作者：
Stoute, JA
影响因子：
82.9
作者：
通讯作者：
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