Mias George I, Chen Rui, Zhang Yan, Sridhar Kunju, Sharon Donald, Xiao Li, Im Hogune, Snyder Michael P, Greenberg Peter L
1] Department of Genetics, Stanford University School of Medicine, Stanford, California, USA [2].
Sci Rep. 2013 Nov 22;3:3311. doi: 10.1038/srep03311.
Increased autoantibody reactivity in plasma from Myelodysplastic Syndromes (MDS) patients may provide novel disease signatures, and possible early detection. In a two-stage study we investigated Immunoglobulin G reactivity in plasma from MDS, Acute Myeloid Leukemia post MDS patients, and a healthy cohort. In exploratory Stage I we utilized high-throughput protein arrays to identify 35 high-interest proteins showing increased reactivity in patient subgroups compared to healthy controls. In validation Stage II we designed new arrays focusing on 25 of the proteins identified in Stage I and expanded the initial cohort. We validated increased antibody reactivity against AKT3, FCGR3A and ARL8B in patients, which enabled sample classification into stable MDS and healthy individuals. We also detected elevated AKT3 protein levels in MDS patient plasma. The discovery of increased specific autoantibody reactivity in MDS patients, provides molecular signatures for classification, supplementing existing risk categorizations, and may enhance diagnostic and prognostic capabilities for MDS.
骨髓增生异常综合征（MDS）患者血浆中自身抗体反应性增加可能提供新的疾病特征及早期检测的可能性。在一项两阶段研究中，我们调查了MDS患者、MDS后急性髓系白血病患者以及健康队列血浆中的免疫球蛋白G反应性。在探索性的第一阶段，我们利用高通量蛋白质阵列来识别35种高关注度蛋白质，这些蛋白质在患者亚组中与健康对照相比显示出增加的反应性。在验证性的第二阶段，我们设计了新的阵列，聚焦于第一阶段鉴定出的25种蛋白质，并扩大了初始队列。我们验证了患者针对AKT3、FCGR3A和ARL8B的抗体反应性增加，这使得能够将样本分类为稳定的MDS患者和健康个体。我们还检测到MDS患者血浆中AKT3蛋白水平升高。MDS患者中特异性自身抗体反应性增加的发现，为分类提供了分子特征，补充了现有的风险分类，并可能增强MDS的诊断和预后能力。
