Department of Pediatrics, The Affiliated Huaian No.1 People's Hospital of Nanjing Medical University, Huai'an, China.
Department of Neonatology, The Affiliated Huaian No.1 People's Hospital of Nanjing Medical University, Huai'an, China.
Front Immunol. 2023 Dec 14;14:1301227. doi: 10.3389/fimmu.2023.1301227. eCollection 2023.
Primary immune thrombocytopenia (ITP) is the most common acquired autoimmune bleeding disorder among children. While glucocorticoids are the primary first-line treatment for ITP treatment, they prove ineffective in certain patients. The challenge of identifying biomarkers capable of early prediction regarding the response to glucocorticoid therapy in ITP persists. This study aimed to identify ideal biomarkers for predicting glucocorticoid efficacy in patients with ITP using plasma proteomics.
A four-dimensional data-independent acquisition approach was performed to determine the differentially expressed proteins in plasma samples collected from glucocorticoid-sensitive (GCS) (n=18) and glucocorticoid-resistant (GCR) (n=17) children with ITP treated with prednisone. The significantly differentially expressed proteins were selected for enzyme-linked immunosorbent assay validation in a cohort conprising 65 samples(30 healthy controls, 18 GCS and 17 GCR children with ITP). Receiver operating characteristics curves, calibration curves, and clinical decision curve analysis were used to determine the diagnostic efficacy of this method.
47 differentially expressed proteins (36 up-regulated and 11 down-regulated) were identified in the GCR group compared with the GCS group. The significantly differentially expressed proteins myosin heavy chain 9 (MYH9) and fetuin B (FETUB) were selected for enzyme-linked immunosorbent assay validation. The validation results were consistent with the proteomics analyses. Compared with the GCS group, the GCR group exhibited a significantly reduced the plasma concentration of MYH9 and elevated the plasma concentration of FETUB. Furthermore, the receiver operating characteristics curves, calibration curves, and clinical decision curve analysis demonstrated good diagnostic efficacy of these validated biomarkers.
This study contributes to the establishment of objective biological indicators for precision therapy in children with ITP. More importantly, the proteins MYH9 and FETUB hold potential as a foundation for making informed decisions regarding alternative treatments for drugresistant patients, thereby preventing treatment delays.
原发性免疫性血小板减少症（ITP）是儿童中最常见的获得性自身免疫性出血性疾病。虽然糖皮质激素是 ITP 的主要一线治疗药物，但在某些患者中无效。因此，仍需要寻找能够早期预测 ITP 患者对糖皮质激素治疗反应的生物标志物。本研究旨在使用血浆蛋白质组学方法寻找预测 ITP 患者糖皮质激素疗效的理想生物标志物。
采用四维度数据非依赖性采集方法检测泼尼松治疗的糖皮质激素敏感（GCS）（n=18）和糖皮质激素抵抗（GCR）（n=17）儿童的血浆样本中的差异表达蛋白。选择差异表达蛋白进行酶联免疫吸附试验验证，验证队列包括 65 例样本（30 例健康对照，18 例 GCS 和 17 例 GCR 儿童 ITP）。采用受试者工作特征曲线、校准曲线和临床决策曲线分析来确定该方法的诊断效能。
与 GCS 组相比，GCR 组有 47 个差异表达蛋白（36 个上调，11 个下调）。差异表达蛋白肌球蛋白重链 9（MYH9）和胎球蛋白 B（FETUB）被选择进行酶联免疫吸附试验验证。验证结果与蛋白质组学分析一致。与 GCS 组相比，GCR 组的 MYH9 血浆浓度显著降低，FETUB 血浆浓度显著升高。此外，受试者工作特征曲线、校准曲线和临床决策曲线分析表明，这些验证后的生物标志物具有良好的诊断效能。
本研究为儿童 ITP 的精准治疗建立了客观的生物学指标。更重要的是，MYH9 和 FETUB 蛋白可作为制定耐药患者替代治疗决策的基础，从而避免治疗延误。
