Identification of novel biomarkers in chronic immune thrombocytopenia (ITP) by microarray‐based serum protein profiling
Identification of novel biomarkers in chronic immune thrombocytopenia (ITP) by microarray‐based serum protein profiling
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DOI：
10.1111/bjh.13861
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发表时间：
2016-02
影响因子：
6.5
通讯作者：
Gürkan Bal;M. Futschik;D. Hartl;F. Ringel;Julian Kamhieh-Milz;V. Sterzer;J. Hoheisel;M. S. Alhamdani;A. Salama
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文献类型：
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作者：
Gürkan Bal;M. Futschik;D. Hartl;F. Ringel;Julian Kamhieh-Milz;V. Sterzer;J. Hoheisel;M. S. Alhamdani;A. Salama
免疫性血小板减少症（ITP）的病理机制尚不清楚，其诊断仍然是一个排除的过程。目前，尚无已知的ITP特异性生物标志物来支持鉴别诊断和治疗决策。血清蛋白质的分析对于鉴定这些生物标志物可能是有价值的。使用755种抗体的微阵列分析了46例原发性慢性ITP患者和34例健康献血员的血清。我们鉴定了161个差异表达蛋白。除了癌蛋白和肿瘤抑制蛋白，包括凋亡调节因子BCL 2、乳腺癌1型易感蛋白（BRCA 1）、范可尼贫血互补组C（FANCC）和血管内皮生长因子A（VEGFA），我们还在ITP患者亚组中检测到6种抗核自身抗体：抗PCNA、抗SmD、抗Ro/SSA 60、抗Ro/SSA 52、抗La/SSB和抗RNPC抗体。这一发现可能为ITP与恶性肿瘤和其他自身免疫性疾病的关联提供了合理的解释。虽然RUNX 1 mRNA在患者外周血单核细胞（PBMC）中的表达显著下调，但在ITP患者的血小板中观察到RUNX 1蛋白的积累。这可能表明PBMC和巨核细胞中RUNX 1表达失调，并可能导致免疫应答失衡和血小板生成受损。总之，我们提供了新的见解ITP的致病机制，值得进一步探索。
The pathological mechanisms underlying the development of immune thrombocytopenia (ITP) are unclear and its diagnosis remains a process of exclusion. Currently, there are no known specific biomarkers for ITP to support differential diagnosis and treatment decisions. Profiling of serum proteins may be valuable for identifying such biomarkers. Sera from 46 patients with primary chronic ITP and 34 healthy blood donors were analysed using a microarray of 755 antibodies. We identified 161 differentially expressed proteins. In addition to oncoproteins and tumour‐suppressor proteins, including apoptosis regulator BCL2, breast cancer type 1 susceptibility protein (BRCA1), Fanconi anaemia complementation group C (FANCC) and vascular endothelial growth factor A (VEGFA), we detected six anti‐nuclear autoantibodies in a subset of ITP patients: anti‐PCNA, anti‐SmD, anti‐Ro/SSA60, anti‐Ro/SSA52, anti‐La/SSB and anti‐RNPC antibodies. This finding may provide a rational explanation for the association of ITP with malignancies and other autoimmune diseases. While RUNX1mRNA expression in the peripheral blood mononuclear cells (PBMC) of patients was significantly downregulated, an accumulation of RUNX1 protein was observed in the platelets of ITP patients. This may indicate dysregulation of RUNX1 expression in PBMC and megakaryocytes and may lead to an imbalanced immune response and impaired thrombopoiesis. In conclusion, we provide novel insights into the pathogenic mechanisms of ITP that warrant further exploration.