title: Hematopoietic stem cell transplantation induces immunologic tolerance in renal transplant patients via modulation of inflammatory and repair processes.
abstract: 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. Investigation 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.
  
  
  CONCLUSIONS
  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.
authors.affiliation: Qingpu Branch, Fudan University Zhongshan Hospital, Shanghai, China.
authors.forename: Duojiao
authors.initials: D
authors.lastname: Wu
authors.forename: Guisheng
authors.initials: G
authors.lastname: Qi
authors.forename: Xuanchuan
authors.initials: X
authors.lastname: Wang
authors.forename: Ming
authors.initials: M
authors.lastname: Xu
authors.forename: Ruiming
authors.initials: R
authors.lastname: Rong
authors.forename: Xiangdong
authors.initials: X
authors.lastname: Wang
authors.forename: Tongyu
authors.initials: T
authors.lastname: Zhu
mesh_terms: D000328:Adult; D002853:Chromatography, Liquid; D004797:Enzyme-Linked Immunosorbent Assay; D005260:Female; D018380:Hematopoietic Stem Cell Transplantation; D006801:Humans; D007108:Immune Tolerance; D007249:Inflammation / Q000473:pathology*; D016030:Kidney Transplantation / Q000276:immunology*; D008297:Male; D053719:Tandem Mass Spectrometry