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Proteomic Analysis of PBMC from Patients with Systemic Lupus Erythematosus

Author: ZhouDi
Tutor: HaoFei
School: Third Military Medical University
Course: Dermatology and Venereology
Keywords: Systemic Lupus Erythematosus Peripheral blood mononuclear cells Proteome Two-dimensional electrophoresis High performance liquid chromatography ion trap tandem mass spectrometry
CLC: R593.241
Type: Master's thesis
Year: 2008
Downloads: 120
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Abstract


Objective: systemic lupus erythematosus typical autoimmune diseases, the elucidation of the pathophysiological mechanisms and disease clearly define the proposed has been the complexity of clinical symptoms and multiple organ system involvement hinder. The current diagnostic criteria rely on clinical symptoms without emphasis on the development of the disease process itself immune status, and subjective clinical symptoms judgment: early atypical symptoms overlooked, once the typical clinical symptoms, the patient often has been accompanied by organic disease or decompensated damage to the immune system and vital organs, the prognosis greatly decreased, an urgent need accurate and effective method of early diagnosis. Proteomics, molecular biology in recent years, new technology has brought a new approach for autoimmune mechanism clarified. With the the proteomics technology advances, a comprehensive study of the disease protein levels, the subjects in the analysis of the pathological mechanisms of SLE, improve early diagnosis and detection of disease-specific markers to identify therapeutic targets and drug development exhibit unique advantages and prospects. Currently, most of the research has focused on these two specimens of serum, urine, compared to the field of study of the extracellular fluid, intracellular immune cells proteomics research is still in a relatively empty. Variety of immune events involved in the pathogenesis of SLE, contains a variety of immune cells are involved. T, B, NK cells and other immune cells, including peripheral blood mononuclear cells (PBMC) as a starting point to do a study on SLE PBMC protein using proteomic methods study SLE The early onset and provide the basis for suggesting that disease activity. Methods: 14 patients with SLE were extracted and nine healthy donors of PBMC proteome using two-dimensional electrophoresis separation, high-performance liquid chromatography ion trap some of the differences are significant, highly repetitive proteins concatenation mass spectrometry (Ion Trap HPLC-Chip-MS/MS), the determination of its peptide sequence tags Figure (PST), differences in Internet protein database searches identified proteins. Results: 1. Reproducible dimensional electrophoresis profiles. The image analysis: an SLE patients and four healthy donors PBMC protein match points to 1084, the high expression of SLE and specific expression of protein spots 71 and 17, high expression of healthy blood donors and specifically expressed protein spots 45 and 20. MS analysis on a high reproducibility of differential expression of 30 protein spots after database searches identified 28 proteins PST, corresponding to 27 proteins, respectively, as follows: 3 - phosphate dehydrogenase, tyrosine acid translation synthase, glycogen phosphorylase, transketolase, pyruvate kinase M1/M2 isozyme, triose phosphate isomerase, elongation factor 1α1 phosphoglycerate kinase 1, alpha enolase, spot associated protein, gelsolin precursor, proline serine threonine phosphatase interacting protein 2, adenylate cyclase-associated protein 1, filamin C filamin A WD repeat-containing protein 1 ankle protein 1, microtubule protein β chain, integrin-coupled protein kinase, PDZ-LIM domain protein, protein tyrosine kinase CSK osteoclast stimulating factor 1, a membrane-associated protein A5 T the complex protein Iζ Asian units heat shock protein β1 heat shock cognate protein 71, and I kind of dynein protein. Or specifically expressed in PBMC of SLE patients in high there gelsolin precursor, phosphoglycerate kinase 1, WD repeat containing protein 1 alpha enolase, osteoclast stimulating factor 1, tubulin beta chain, annexin protein A5 and heat shock cognate protein 71 Class 8 protein, and the rest are in the SLE patients reduced expression or non-expression. Conclusion: The application of proteomics technology to conduct a preliminary screening and identification of specific proteins in patients with SLE PBMCs found triosephosphate isomerase, annexin A5, heat shock cognate protein 71 27 associated with the pathogenesis of SLE may become SLE biological tagged proteins. SLE patients with different clinical syndromes there may be specific biological tags, the some biological labels only appear in a specific clinical syndrome, but its better certainty needed follow-up experiments to verify. SLE patients PBMC proteomics is likely to in-depth study of its pathogenesis, the establishment of new diagnostic indicators provide a good platform.

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CLC: > Medicine, health > Internal Medicine > Systemic disease > Autoimmune diseases > Autoimmune diseases, connective tissue disease > Lupus erythematosus > Systemic lupus erythematosus
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