Divergent Directionality of Immune Cell-Specific Protein Expression between Bipolar Lithium Responders and Non-Responders Revealed by Enhanced Flow Cytometry.
Divergent Directionality of Immune Cell-Specific Protein Expression between Bipolar Lithium Responders and Non-Responders Revealed by Enhanced Flow Cytometry.
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DOI：
10.3390/medicina59010120
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发表时间：
2023-01-07
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背景和目的：目前还没有生物标志物来预测锂的反应。本研究使用CellPrint™增强流式细胞术研究了双相情感障碍（BD）患者锂治疗前后单核细胞和CD 4+淋巴细胞中代表细胞通路谱的28种蛋白质。材料与方法：对有症状的BD I型或II型患者，给予锂剂治疗（血清锂浓度≥ 0.6mEq/L）16周。采用标准评定量表对患者进行评估，并将其分为两组，应答者（较基线改善≥50%）和无应答者。用CellPrint™（一种增强型流式细胞术程序）分析了CD 4+淋巴细胞和单核细胞中的28种细胞内蛋白。分析数据中蛋白质表达水平的差异。结果如下：意向治疗样本包括13例锂应答者（12例治疗前和9例治疗后血样）和11例锂无应答者（11例治疗前和4例治疗后血样）。在锂处理之前，未观察到组间表达的显著差异。治疗后，大多数分析物在应答者中的表达增加，而在非应答者中的表达减少。在应答者中观察到PDEB 4和NR 3C 1的显著增加。在无应答者中观察到NR 3C 1显著降低。结论：锂诱导蛋白质表达的发散方向性取决于患者是否为应答者或非应答者，阐明了锂应答性的分子特征。随后需要进行更大样本量的研究。
Background and Objectives: There is no biomarker to predict lithium response. This study used CellPrint™ enhanced flow cytometry to study 28 proteins representing a spectrum of cellular pathways in monocytes and CD4+ lymphocytes before and after lithium treatment in patients with bipolar disorder (BD). Materials and Methods: Symptomatic patients with BD type I or II received lithium (serum level ≥ 0.6 mEq/L) for 16 weeks. Patients were assessed with standard rating scales and divided into two groups, responders (≥50% improvement from baseline) and non-responders. Twenty-eight intracellular proteins in CD4+ lymphocytes and monocytes were analyzed with CellPrint™, an enhanced flow cytometry procedure. Data were analyzed for differences in protein expression levels. Results: The intent-to-treat sample included 13 lithium-responders (12 blood samples before treatment and 9 after treatment) and 11 lithium-non-responders (11 blood samples before treatment and 4 after treatment). No significant differences in expression between the groups was observed prior to lithium treatment. After treatment, the majority of analytes increased expression in responders and decreased expression in non-responders. Significant increases were seen for PDEB4 and NR3C1 in responders. A significant decrease was seen for NR3C1 in non-responders. Conclusions: Lithium induced divergent directionality of protein expression depending on the whether the patient was a responder or non-responder, elucidating molecular characteristics of lithium responsiveness. A subsequent study with a larger sample size is warranted.
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6
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