Haptoglobin 1 allele predicts higher serum haptoglobin concentration and lower multiorgan failure risk in sickle cell disease.
Haptoglobin 1 allele predicts higher serum haptoglobin concentration and lower multiorgan failure risk in sickle cell disease.
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Haptoglobin 1等位基因预测镰状细胞疾病中较高的血清Haptoglobin浓度和较低的多器官衰竭风险。
DOI：
10.1182/bloodadvances.2022007980
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发表时间：
2022-12-27
期刊：
影响因子：
7.5
通讯作者：
Saraf, Santosh L.
中科院分区：
文献类型：
--
作者：
Ruiz, Maria A.;Shah, Binal N.;Ren, Guohui;Hussain, Faiz;Njoku, Franklin;Machado, Roberto F.;Gordeuk, Victor R.;Saraf, Santosh L.
患有 SCD 和 HP 1 等位基因的成年人在稳态和血管闭塞期间具有较低的无细胞血红蛋白与 HP 比率。 HP 1 等位基因与纵向随访中多器官衰竭风险降低一倍相关。触珠蛋白（HP）是一种急性时相蛋白，也是无细胞血红蛋白的主要清除剂。当 HP 耗尽时，如在镰状细胞病 (SCD) 等溶血性疾病中观察到的那样，无细胞血红蛋白会导致急性器官损伤。 HP 1-1、2-1 和 2-2 同工型对 HP 和无细胞血红蛋白浓度以及 SCD 相关并发症的影响尚不清楚。在 SCD 患者的纵向队列中，HP 1 等位基因与常规就诊以及因血管闭塞发作或急性胸部综合征住院期间较高的 HP 和较低的无细胞血红蛋白浓度相关。中位随访时间为 6.8 年，在 391 名 SCD 患者中，42% (n = 163) 发生急性胸部综合征，14% (n = 53) 发生多器官衰竭，随访时间最短为 6 个月。 HP 1 等位基因与急性胸部综合征期间发生多器官衰竭的较低风险独立相关（加法模型风险比，0.5；P < .001）。未来的研究根据 HP 基因型评估 HP 浓度的调节和结合无细胞血红蛋白的能力，可能有助于识别多器官衰竭高风险的 SCD 患者，并指导干预措施，例如快速开始换血或 HP 替代治疗。
Adults with SCD and HP 1 allele have lower cell-free hemoglobin-to-HP ratios at steady state and during a vaso-occlusive episode. The HP 1 allele is associated with a twofold lower risk of multiorgan failure on longitudinal follow-up. Haptoglobin (HP) is an acute-phase protein and the main scavenger of cell-free hemoglobin. When HP is depleted, as observed in hemolytic conditions such as sickle cell disease (SCD), cell-free hemoglobin can lead to acute organ damage. The impact of the HP 1-1, 2-1, and 2-2 isoforms on HP and cell-free hemoglobin concentrations and SCD-related complications is unclear. In a longitudinal cohort of patients with SCD, the HP 1 allele was associated with higher HP and lower cell-free hemoglobin concentrations at a routine clinic visit as well as during hospitalization for a vaso-occlusive episode or acute chest syndrome. With a median follow-up of 6.8 years, acute chest syndrome occurred in 42% (n = 163) and multiorgan failure in 14% (n = 53) of 391 patients with SCD with a minimum follow-up of 6 months. The HP 1 allele was independently associated with lower risk of developing multiorgan failure during acute chest syndrome (additive model hazard ratio, 0.5; P < .001). Future studies assessing the regulation of HP concentrations and ability to bind cell-free hemoglobin according to the HP genotype may help to identify patients with SCD at high risk for multiorgan failure and to guide interventions, such as rapid initiation of exchange transfusion or HP replacement therapy.
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影响因子：
1
作者：
Meher, Satyabrata;Mohanty, Pradeep K.;Dash, Bisnu P.
通讯作者：
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影响因子：
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作者：
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通讯作者：
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影响因子：
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影响因子：
15.1
作者：
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