In-depth proteomic analysis of juvenile dermatomyositis serum reveals protein expression associated with muscle-specific autoantibodies
In-depth proteomic analysis of juvenile dermatomyositis serum reveals protein expression associated with muscle-specific autoantibodies
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对幼年皮肌炎血清的深入蛋白质组学分析揭示了与肌肉特异性自身抗体相关的蛋白质表达
DOI：
10.1093/rheumatology/kead165
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发表时间：
2023
期刊：
影响因子：
5.5
通讯作者：
Akioka Shinji
中科院分区：
文献类型：
--
作者：
Sato Hironori;Inoue Yuzaburo;Kawashima Yusuke;Konno Ryo;Ohara Osamu;Kuwana Masataka;Kobayashi Norimoto;Takezaki Shunichiro;Akioka Shinji
目的JDM的临床症状和并发症因肌肉特异性自身抗体（MSA）的类型而异。我们的目的是通过全面分析JDM患者血清中存在的蛋白质来鉴定表征各种临床特征的MSA特异性蛋白质表达谱。我们分析了来自抗黑色素瘤分化相关蛋白5（MDA 5）抗体阳性的JDM患者的血清（n= 5），抗核基质蛋白2（NXP 2）抗体（n= 5）和抗转录中间因子1 α或γ亚基（TIF 1-γ）抗体（n= 5），并通过单次液相色谱-串联质谱法（MS）以数据独立采集模式评估健康对照（n= 5），其对于比较定量分析是上级的。我们确定了不同的蛋白质组的基础上，MSAs和进行通路分析，以了解他们的characteristic.ResultsWe检测到2413蛋白质从血清MS分析，508蛋白质通常改变的MSAs，包括许多肌生成酶和IFN-调节蛋白。使用前50名的蛋白质，在每个MSA组上调的途径分析显示，I型IFN和蛋白酶体途径显着上调在抗-MDA 5抗体groups.ConclusionAlthough JDM血清中含有许多蛋白质通常改变的MSA，与临床特征的MSA不同的蛋白质积累的基础上的途径。与MSA相关的深入血清蛋白质谱可能有助于开发治疗靶分子和生物标志物。
ObjectivesThe clinical symptoms and complications of JDM differ depending on the type of muscle-specific autoantibodies (MSAs) present. We aimed to identify protein expression profiles specific for MSAs that characterize various clinical features by comprehensively analyzing the proteins present in the serum of patients with JDM.MethodsWe analysed sera from patients with JDM that were positive for anti–melanoma differentiation–associated protein 5 (MDA5) antibodies (n= 5), anti–nuclear matrix protein 2 (NXP2) antibodies (n= 5) and anti–transcriptional intermediary factor 1 alpha or gamma subunit (TIF1-γ) antibodies (n= 5), and evaluated healthy controls (n= 5) via single-shot liquid chromatography-tandem mass spectrometry (MS) in data-independent acquisition mode, which is superior for comparative quantitative analysis. We identified different protein groups based on MSAs and performed pathway analysis to understand their characteristics.ResultsWe detected 2413 proteins from serum MS analysis; 508 proteins were commonly altered in MSAs, including many myogenic enzymes and IFN-regulated proteins. Pathway analysis using the top 50 proteins that were upregulated in each MSA group revealed that the type I IFN and proteasome pathways were significantly upregulated in the anti-MDA5 antibody group alone.ConclusionAlthough JDM serum contains many proteins commonly altered in MSAs, the pathways associated with clinical features of MSAs differ based on protein accumulation. In-depth serum protein profiles associated with MSAs may be useful for developing therapeutic target molecules and biomarkers.