Hematopoietic stem cell transplantation induces immunologic tolerance in renal transplant patients via modulation of inflammatory and repair processes
<p>Abstract</p> <p>Background</p> <p>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 i...
| Main Authors: | , , , , , , |
|---|---|
| Format: | Article |
| Language: | English |
| Published: |
BMC
2012-08-01
|
| Series: | Journal of Translational Medicine |
| Subjects: | |
| Online Access: | http://www.translational-medicine.com/content/10/1/182 |
| _version_ | 1818757612228837376 |
|---|---|
| author | Wu Duojiao Qi Guisheng Wang Xuanchuan Xu Ming Rong Ruiming Wang Xiangdong Zhu Tongyu |
| author_facet | Wu Duojiao Qi Guisheng Wang Xuanchuan Xu Ming Rong Ruiming Wang Xiangdong Zhu Tongyu |
| author_sort | Wu Duojiao |
| collection | DOAJ |
| description | <p>Abstract</p> <p>Background</p> <p>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.</p> <p>Methods</p> <p>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.</p> <p>Results and Discussion</p> <p>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.</p> <p>Conclusions</p> <p>Thus, our study provides new insight into the molecular events in the hematopoietic stem cell-induced immunologic tolerance.</p> |
| first_indexed | 2024-12-18T06:13:42Z |
| format | Article |
| id | doaj.art-4b4c14cf9c3c4d989289a3054ca577ea |
| institution | Directory Open Access Journal |
| issn | 1479-5876 |
| language | English |
| last_indexed | 2024-12-18T06:13:42Z |
| publishDate | 2012-08-01 |
| publisher | BMC |
| record_format | Article |
| series | Journal of Translational Medicine |
| spelling | doaj.art-4b4c14cf9c3c4d989289a3054ca577ea2022-12-21T21:18:19ZengBMCJournal of Translational Medicine1479-58762012-08-0110118210.1186/1479-5876-10-182Hematopoietic stem cell transplantation induces immunologic tolerance in renal transplant patients via modulation of inflammatory and repair processesWu DuojiaoQi GuishengWang XuanchuanXu MingRong RuimingWang XiangdongZhu Tongyu<p>Abstract</p> <p>Background</p> <p>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.</p> <p>Methods</p> <p>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.</p> <p>Results and Discussion</p> <p>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.</p> <p>Conclusions</p> <p>Thus, our study provides new insight into the molecular events in the hematopoietic stem cell-induced immunologic tolerance.</p>http://www.translational-medicine.com/content/10/1/182Kidney transplantationImmunologic rejectionImmunologic toleranceHematopoietic stem cell transplantationProteome |
| spellingShingle | Wu Duojiao Qi Guisheng Wang Xuanchuan Xu Ming Rong Ruiming Wang Xiangdong Zhu Tongyu Hematopoietic stem cell transplantation induces immunologic tolerance in renal transplant patients via modulation of inflammatory and repair processes Journal of Translational Medicine Kidney transplantation Immunologic rejection Immunologic tolerance Hematopoietic stem cell transplantation Proteome |
| title | Hematopoietic stem cell transplantation induces immunologic tolerance in renal transplant patients via modulation of inflammatory and repair processes |
| title_full | Hematopoietic stem cell transplantation induces immunologic tolerance in renal transplant patients via modulation of inflammatory and repair processes |
| title_fullStr | Hematopoietic stem cell transplantation induces immunologic tolerance in renal transplant patients via modulation of inflammatory and repair processes |
| title_full_unstemmed | Hematopoietic stem cell transplantation induces immunologic tolerance in renal transplant patients via modulation of inflammatory and repair processes |
| title_short | Hematopoietic stem cell transplantation induces immunologic tolerance in renal transplant patients via modulation of inflammatory and repair processes |
| title_sort | hematopoietic stem cell transplantation induces immunologic tolerance in renal transplant patients via modulation of inflammatory and repair processes |
| topic | Kidney transplantation Immunologic rejection Immunologic tolerance Hematopoietic stem cell transplantation Proteome |
| url | http://www.translational-medicine.com/content/10/1/182 |
| work_keys_str_mv | AT wuduojiao hematopoieticstemcelltransplantationinducesimmunologictoleranceinrenaltransplantpatientsviamodulationofinflammatoryandrepairprocesses AT qiguisheng hematopoieticstemcelltransplantationinducesimmunologictoleranceinrenaltransplantpatientsviamodulationofinflammatoryandrepairprocesses AT wangxuanchuan hematopoieticstemcelltransplantationinducesimmunologictoleranceinrenaltransplantpatientsviamodulationofinflammatoryandrepairprocesses AT xuming hematopoieticstemcelltransplantationinducesimmunologictoleranceinrenaltransplantpatientsviamodulationofinflammatoryandrepairprocesses AT rongruiming hematopoieticstemcelltransplantationinducesimmunologictoleranceinrenaltransplantpatientsviamodulationofinflammatoryandrepairprocesses AT wangxiangdong hematopoieticstemcelltransplantationinducesimmunologictoleranceinrenaltransplantpatientsviamodulationofinflammatoryandrepairprocesses AT zhutongyu hematopoieticstemcelltransplantationinducesimmunologictoleranceinrenaltransplantpatientsviamodulationofinflammatoryandrepairprocesses |