Hagiwara Sho, Shiohama Tadashi, Takahashi Satoru, Ishikawa Masaki, Kawashima Yusuke, Sato Hironori, Sawada Daisuke, Uchida Tomoko, Uchikawa Hideki, Kobayashi Hironobu, Shiota Megumi, Nabatame Shin, Tsujimura Keita, Hamada Hiromichi, Suzuki Keiichiro
Department of Pediatrics, Graduate School of Medicine, Chiba University, 1-8-1 Inohana, Chuo-ku, Chiba-shi 260-0856, Chiba, Japan.
Department of Pediatrics, Asahikawa Medical University, 2-1-1-1 Midorigaoka Higashi, Asahikawa City 078-8510, Hokkaido, Japan.
Biomedicines. 2024 Sep 24;12(10):2172. doi: 10.3390/biomedicines12102172.
Rett syndrome is a neurodevelopmental disorder that affects 1 in 10,000 females. Various treatments have been explored; however, no effective treatments have been reported to date, except for trofinetide, a synthetic analog of glycine-proline-glutamic acid, which was approved by the FDA in 2023. Serological biomarkers that correlate with the disease status of RTT are needed to promote early diagnosis and to develop novel agents. In this study, we performed a high-depth proteomic analysis of extracellular vesicles containing preparations extracted from patient plasma samples to identify novel biomarkers. We identified 33 upregulated and 17 downregulated candidate proteins among a total of 4273 proteins in RTT compared to the healthy controls. Among these, UBE3B was predominantly increased in patients with Rett syndrome and exhibited a strong correlation with the clinical severity score, indicating the severity of the disease. We demonstrated that the proteomics of high-depth extracellular vesicles containing preparations in rare diseases could be valuable in identifying new disease biomarkers and understanding their pathophysiology.
雷特综合征是一种神经发育障碍疾病，每10000名女性中就有1人受其影响。人们已经探索了各种治疗方法；然而，迄今为止，除了曲非奈肽（一种甘氨酸-脯氨酸-谷氨酸的合成类似物，于2023年获得美国食品药品监督管理局批准）外，尚未有有效治疗方法的报道。需要与雷特综合征疾病状态相关的血清生物标志物来促进早期诊断并开发新型药物。在本研究中，我们对从患者血浆样本中提取的含细胞外囊泡制剂进行了深度蛋白质组学分析，以鉴定新型生物标志物。与健康对照相比，我们在雷特综合征患者共4273种蛋白质中鉴定出33种上调和17种下调的候选蛋白质。其中，泛素蛋白连接酶E3B在雷特综合征患者中显著增加，并且与临床严重程度评分呈强相关，表明了疾病的严重程度。我们证明，罕见病中含高深度细胞外囊泡制剂的蛋白质组学对于鉴定新的疾病生物标志物和理解其病理生理学可能具有重要价值。
