Hematopoietic stem cell transplantation induces immunologic tolerance in renal transplant patients via modulation of inflammatory and repair processes

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• 作者：Duojiao Wu (1) (3)
  Guisheng Qi (2) (3)
  Xuanchuan Wang (2) (3)
  Ming Xu (2) (3)
  Ruiming Rong (2) (3)
  Xiangdong Wang (3)
  Tongyu Zhu (1) (2) (3)
  
• 关键词：Kidney transplantation ; Immunologic rejection ; Immunologic tolerance ; Hematopoietic stem cell transplantation ; Proteome
• 刊名：Journal of Translational Medicine
• 出版年：2012
• 出版时间：December 2012
• 年：2012
• 卷：10
• 期：1
• 全文大小：461KB
• 参考文献：1. Sykes M, Sachs DH: Mixed chimerism. / Philos Trans R Soc Lond B Biol Sci 2001, 356:707-26. CrossRef
  2. Field EH, Strober S: Tolerance, mixed chimerism and protection against graftversus-host disease after total lymphoid irradiation. / Philos Trans R Soc Lond B Biol Sci 2001, 356:739-48. CrossRef
  3. Sykes M: / Mixed chimerism and transplant tolerance. Immunity. 2001, 14:417-24.
  4. Scandling JD, Busque S, Dejbakhsh-Jones S: Tolerance and chimerism after renal and hematopoietic-cell transplantation. / N Engl J Med 2008, 358:362-68. CrossRef
  5. Kaplan HS, Rosenberg SA: Extended field radical radiotherapy in advanced Hodgkin’s disease: short-term results of 2 randomized clinical trials. / Cancer Res 1966, 26:1268-276.
  6. Strober S, Dhillon M, Schubert M: Acquired immune tolerance of cadaveric renal allografts: a study of three patients treated with total lymphoid irradiation. / N Engl J Med 1989, 321:28-3. CrossRef
  7. Lowsky R, Takahashi T, Liu YP: Protective conditioning for acute graft- versus-host disease. / N Engl J Med 2005, 353:1321-331. CrossRef
  8. Wu D, Zhu D, Xu M: Analysis of transcriptional factors and regulation networks in patients with acute renal allograft rejection. / J Proteome Res 2011, 10:175-81. CrossRef
  9. Wu WW, Wang G, Baek SJ: Comparative study of three proteomic quantitative methods, DIGE, cICAT, and iTRAQ, using 2D gel- or LC-MALDI TOF/TOF. / J Proteome Res 2006, 5:651-58. CrossRef
  10. Shadforth IP, Dunkley TP, Lilley KS: i-Tracker: for quantitative proteomics using iTRAQ. / BMC Genomics 2005, 6:145. CrossRef
  11. de Boer IH, Astor BC, Kramer H: Lipoprotein abnormalities associated with mild impairment of kidney function in the multi-ethnic study of atherosclerosis. / Clin J Am Soc Nephrol 2008, 3:125-32. CrossRef
  12. Ziegler ME, Chen T, LeBlanc JF: Apolipoprotein A1 and C-terminal fragment of α-1 antichymotrypsin are candidate plasma biomarkers associated with acute renal allograft rejection. / Transplantation 2011, 92:388-95. CrossRef
  13. Garibotto G, Sofia A, Saffioti S: Amino acid and protein metabolism in the human kidney and in patients with chronic kidney disease. / Clin Nutr 2010, 29:424-33. CrossRef
  14. Krishnamoorthy A, Ajay AK, Hoffmann D: Fibrinogen β-derived Bβ(15-2) peptide protects against kidney ischemia/reperfusion injury. / Blood 2011, 118:1934-942. CrossRef
  15. Cattran DC: : Idiopathic membranous glomerulonephritis. / Kidney Int 2001, 59:1983-994. CrossRef
  16. Asgari E, Zhou W, Sacks S: Complement in organ transplantation. / Curr Opin Organ Transplant 2010, 15:486-91. CrossRef
  17. Soto E, Richani K, Romero R: Increased concentration of the complement split product C5a in acute pyelonephritis during pregnancy. / J Matern Fetal Neonatal Med 2005, 17:247-52. CrossRef
  18. Markiewski MM, Nilsson B, Ekdahl KN: Complement and coagulation: strangers or partners in crime? / Trends Immunol 2007, 28:184-92. CrossRef
  19. Ricklin D, Hajishengallis G, Yang K: Complement: a key system for immune surveillance and homeostasis. / Nat Immunol 2010, 11:785-97. CrossRef
  20. Ganter MT, Brohi K, Cohen MJ: Role of the alternative pathway in the early complement activation following major trauma. / Shock 2007, 28:29-4. CrossRef
  21. Ritis K, Doumas M, Mastellos D: A novel C5a receptor-tissue factor cross-talk in neutrophils links innate immunity to coagulation pathways. / J Immunol 2006, 177:4794-802.
  22. Morgan EN, Pohlman TH, Vocelka C: Nuclear factor kappaB mediates a procoagulant response in monocytes during extracorporeal circulation. / J Thorac Cardiovasc Surg. 2003, 125:165-71. CrossRef
  23. Djavani M, Crasta OR, Zhang Y: Gene expression in primate liver during viral hemorrhagic fever. / Virol J. 2009, 6:20. CrossRef
  
• 作者单位：Duojiao Wu (1) (3)
  Guisheng Qi (2) (3)
  Xuanchuan Wang (2) (3)
  Ming Xu (2) (3)
  Ruiming Rong (2) (3)
  Xiangdong Wang (3)
  Tongyu Zhu (1) (2) (3)
  
  1. Qingpu Branch, Fudan University Zhongshan Hospital, Shanghai, China
  3. Shanghai Key Laboratory of Organ Transplantation, Shanghai, China
  2. Department of Urology, Fudan University Zhongshan Hospital, Shanghai, China
  

文摘

Background Inducing donor-specific tolerance in renal transplant patients could potentially prevent allograft rejection and calcineurin inhibitor nephrotoxicity. Combined kidney and hematopoietic stem cell transplant from an HLA-matched donor is an exploratory and promising therapy to induce immune tolerance. Investigtion of molecular mechanisms involved in the disease is needed to understand the potential process of cell therapy and develop strategies to prevent this immunologic rejection. Methods We enrolled nine patients in a clinical study in which cryopreserved donor hematopoietic stem cells were infused on days 2, 4, and 6 after kidney transplantation. One month post-transplant, 4 plasma samples were collected from combined transplants (C-?Tx), and 8 plasma samples from patients with kidney transplantation alone (Tx). High abundance proteins in plasma were depleted and the two-dimensional liquid chromatography-tandem mass spectrometry coupled with iTRAQ labeling was utilized to identify the protein profiling between the two groups. Clusters of up- and down-regulated protein profiles were submitted to MetaCore for the construction of transcriptional factors and regulation networks. Results and Discussion Among the 179 identified proteins, 65 proteins were found in C-?Tx with at least a 2-fold change as compared with Tx. A subset of proteins related to the complement and coagulation cascade, including complement C3a,complement C5a, precrusors to fibrinogen alpha and beta chains,was significantly downregulated in C-?Tx. Meanwhile, Apolipoprotein-A1(ApoA1), ApoC1, ApoA2, ApoE, and ApoB were significantly lower in Tx compared to C-?Tx. Gene ontology analysis showed that the dominant processes of differentially expressed proteins were associated with the inflammatory response and positive regulation of plasma lipoprotein particle remodeling. Conclusions Thus, our study provides new insight into the molecular events in the hematopoietic stem cell-induced immunologic tolerance.