GlycA is not a useful biomarker of inflammation in sickle cell disease.

GlycA is not a useful biomarker of inflammation in sickle cell disease.
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DOI:
10.1111/ijlh.12907
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发表时间:
2018-12
影响因子:
3
通讯作者:
Thein SL
Thein SL
中科院分区:
医学4区
文献类型:
--
作者:
Weisman JK;Meeks D;Mendelsohn L;Remaley AT;Sampson M;Allen DT;Nichols J;Shet AS;Thein SL

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镰状细胞病(SCD)是一种多系统性疾病,其病理学是由复发性炎症驱动的,特别是在血管闭塞危象期间。GlycA是蛋白质糖化的复合指标,是血管炎症相关疾病的敏感生物标志物。我们确定了GlycA作为SCD炎症生物标志物的效用。分析了两项临床研究招募的SCD患者的储存血浆样本。一项研究包括488例稳态SCD(HbSS、HbSβ0和HbSC)患者样本和52例人种匹配的健康对照。另一项研究包括SCD患者(HbSS)稳态和急性疼痛危象期间的配对血浆样本。使用质子NMR在Vantera®临床分析仪上测量血浆GlycA。我们对SCD患者、健康对照和配对样本进行了比较分析。SCD患者血浆GlycA水平明显低于健康对照组(324.6 ± 70.4 μmol/L vs.386.3 ± 74.6 μmol/L,P < 0.0001)。在同一患者中,急性疼痛危象期间的平均血浆GlycA低于稳态,但差异不显著(300.5 ± 36.3 μmol/L vs 314.2 ± 34.8 μmol/L,P = 0.020)。血浆GlycA与血清LDH呈负相关(P = 0.009)。GlycA不是SCD中炎症的合适生物标志物。我们推测,其信号被溶血所混淆,导致结合珠蛋白的耗尽,结合珠蛋白是复合NMR信号中包含的主要血浆蛋白之一。溶血在急性疼痛危象期间进一步加剧,因此与稳态相比,危象中的GlycA水平较低。
Sickle cell disease (SCD) is a multisystemic disorder, the pathology being driven by recurrent inflammation particularly during a vaso-occlusive crisis. GlycA, a composite measure of protein glycation, is a sensitive biomarker for disorders associated with vascular inflammation. We determined the utility of GlycA as a biomarker of inflammation in SCD. Stored plasma samples from patients with SCD recruited to two clinical studies were analyzed. One study encompasses 488 patient samples with SCD (HbSS, HbSβ0 and HbSC) at steady state and 52 race-matched, healthy controls. The other study included paired plasma samples during steady state and acute pain crisis from (HbSS) patients with SCD. Plasma GlycA was measured using a proton NMR on the Vantera® Clinical Analyzer. We performed analysis comparing patients with SCD, healthy controls, and paired samples analysis. The mean plasma GlycA level was lower in SCD compared with healthy controls (324.6 ± 70.4 μmol/L vs. 386.3 ± 74.6 μmol/L, P < 0.0001). Within the same patient, mean plasma GlycA during acute pain crisis was lower than steady state, although the difference was not significant (300.5 ± 36.3 μmol/L vs 314.2 ± 34.8 μmol/L, P = 0.020). Plasma GlycA correlated inversely with serum LDH (P = 0.009). GlycA is not a suitable biomarker of inflammation in SCD. We surmise that its signal is confounded by hemolysis leading to a depletion of haptoglobin, one of the major plasma proteins included in the composite NMR signal. Hemolysis is further exacerbated during an acute pain crisis, hence the lower GlycA levels in crisis compared to steady state.
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