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Transcellular distribution heterogeneity of Annexin A5 represents a protective response to lupus-related thrombophilia: A pilot Proteomics-based study

外周血单个核细胞 膜联蛋白A5 蛋白质组学 免疫学 医学 生物标志物 膜联蛋白 发病机制 纤维蛋白原 内科学 生物 生物化学 基因 流式细胞术 体外
作者
Di Zhou,Na Luo,Qiao Wu,Yi You,Zhifang Zhai,Zhirong Mou,Yuzhang Wu,Hao Fei
出处
期刊:Biochemical and Biophysical Research Communications [Elsevier BV]
卷期号:420 (2): 357-363 被引量:12
标识
DOI:10.1016/j.bbrc.2012.02.162
摘要

Lupus-related vascular events are becoming a formidable obstacle to the improvement of long-term prognosis of systemic lupus erythematosus (SLE) and the existent findings lack for systematization. Proteomics is a strategic approach but its applications in this regard are rare and primarily involve proteome acquisition or biomarker screening, rather than functional identification. To provide further insight, we investigated the proteomic diversity of peripheral blood mononuclear cells (PBMCs) in SLE and the possible role of the identified Annexin A5 (AnxA5) in pathogenesis. The study involved 214 SLE and 183 healthy women. The two-dimensional electrophoresis gel images showed 649 ± 25 and 676 ± 19 protein spots from the PBMCs of the patients and controls, respectively. From these protein spots, 30 differentially expressed proteins were chosen, and 16 of these proteins were identified by mass spectrometer. Western blotting confirmed the over-expressed candidate, AnxA5, from the PBMCs of the patients (SLE:control = 1.607:1, P = 0.0004), but ELISAs indicated decreased levels of sera AnxA5 in the patients compared to healthy donors (SLE vs. control = 26.8 ± 3.0 vs. 49.0 ± 3.3 ng/mL, P < 0.0001). A positive correlation was demonstrated between the manifestation of thrombosis and AnxA5 (Mann–Whitney Z = −2.084, P = 0.037), not anti-AnxA5, while searching for correlations between clinical parameters and the two molecular levels of patient sera. The coagulation assays using plasma from SLE patients revealed that elevated AnxA5 could shorten prothrombin time, activated partial thromboplastin time and prolonged thrombin time (P < 0.001). Our data demonstrated the proteomic differences in the PBMCs between SLE patients and healthy persons. Moreover, the heterogeneous transcellular distribution, increased intracellular concentrations and decreased serum levels of AnxA5 represent a protective response to lupus-related thrombophilia; AnxA5 mostly participate in the common coagulation pathway in the thrombogenesis of SLE.
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