Department of Neurodevelopmental Medicine, Kennedy Krieger Institute, Baltimore, Maryland, USA.
Department of Neurology, Johns Hopkins University School of Medicine, Baltimore, Maryland, USA.
Proteomics Clin Appl. 2021 Sep;15(5):e2100003. doi: 10.1002/prca.202100003. Epub 2021 May 24.
Sickle cell disease (SCD) is an inherited hemoglobinopathy that causes stroke and silent cerebral infarct (SCI). Our aim was to identify markers of brain injury in SCD.
Plasma proteomes were analyzed using a sequential separation approach of hemoglobin (Hb) and top abundant plasma protein depletion, followed by reverse phase separation of intact proteins, trypsin digestion, and tandem mass spectrometry. We compared plasma proteomes of children with SCD with and without SCI in the Silent Cerebral Infarct Multi-Center Clinical Trial (SIT Trial) to age-matched, healthy non-SCD controls.
From the SCD group, 1172 proteins were identified. Twenty-five percent (289/1172) were solely in the SCI group. Twenty-five proteins with enriched expression in the human brain were identified in the SCD group. Neurogranin (NRGN) was the most abundant brain-enriched protein in plasma of children with SCD. Using a NRGN sandwich immunoassay and SIT Trial samples, median NRGN levels were higher at study entry in children with SCD (0.28 ng/mL, N = 100) compared to control participants (0.12 ng/mL, N = 25, p < 0.0004).
NRGN levels are elevated in children with SCD. NRGN and other brain-enriched plasma proteins identified in plasma of children with SCD may provide biochemical evidence of neurological injury.
镰状细胞病（SCD）是一种遗传性血红蛋白病，可导致中风和无症状性脑梗死（SCI）。我们的目的是确定 SCD 中的脑损伤标志物。
使用血红蛋白（Hb）的顺序分离方法和丰度最高的血浆蛋白耗尽，然后进行完整蛋白质的反相分离、胰蛋白酶消化和串联质谱分析，来分析血浆蛋白质组。我们将 SIT 试验中伴有和不伴有 SCI 的 SCD 儿童与年龄匹配的健康非 SCD 对照者的血浆蛋白质组进行了比较。
从 SCD 组中鉴定出 1172 种蛋白质。25%（289/1172）仅存在于 SCI 组中。在 SCD 组中鉴定出 25 种在人脑中有丰富表达的蛋白质。神经颗粒蛋白（NRGN）是 SCD 儿童血浆中含量最丰富的脑富集蛋白。使用 NRGN 夹心免疫测定法和 SIT 试验样本，SCD 患儿（0.28ng/mL，N=100）研究入组时的中位 NRGN 水平高于对照组参与者（0.12ng/mL，N=25，p<0.0004）。
NRGN 水平在 SCD 儿童中升高。在 SCD 儿童血浆中鉴定出的 NRGN 和其他脑富集血浆蛋白可能为神经损伤提供生化证据。
