Kidney allograft transplantation improved the prognosis and quality of life of patients with end-stage renal diseases but the occurrence of acute rejection represents a limitation of the final outcome. Noninvasive biomarkers are needed as well as further advancements in the understanding of immune mechanisms of reaction to the allograft. Our study of 138 patients focused on one-year monitoring of serum concentrations of 12 chemokines regulating the recruitment of different immune cells into transplanted allograft and on in vitro regulation of the same chemokines release by interactions of renal proximal epithelial cells with monocyte/macrophage cell line stimulated with TNF alpha. In a group of 44 patients with acute rejection, higher serum pretransplant levels of CXCL1, CXCL5, CXCL6, CCL2, CCL21, and particularly CXCL10 and CX3CL1(both p < 0.001) were found suggesting their higher proinflammatory status as compared to subjects with the uncomplicated outcome. In samples collected at the day of biopsy positive for acute rejection, chemokines CXCL9 and CXCL11 attracting preferentially Th1 lymphocytes were found to be upregulated. In our in vitro model with TNF alpha induction, renal proximal epithelial cells seemed to be a more potent source of chemokines attracting neutrophils as compared to monocyte/macrophage cell line but the coculture of these cells potentiated release of neutrophilic chemokines CXCL5 and CXCL6. Similar augmentation of chemokine production was found also in the case of CCL2. On the other hand, adding of monocytes/macrophages to a culture of renal epithelial cells suppressed the release of CXCL10 and CXCL11 attracting T lymphocytes. We assume from our data that in kidney allograft transplantation, chemokines attracting neutrophils, T lymphocytes, and monocytes are induced simultaneously and measurement some of them in combination might be used as biomarkers of acute rejection. Mutual cell-cell interactions of immune cells with renal parenchyma seem to be important for fine regulation of chemokine release.

• MeSH
• alografty MeSH
• chemokin CCL2 krev   MeSH
• chemokin CCL21 krev   MeSH
• chemokin CX3CL1 krev   MeSH
• chemokin CXCL1 krev   MeSH
• chemokin CXCL10 krev   MeSH
• chemokin CXCL11 krev   MeSH
• chemokin CXCL5 krev   MeSH
• chemokin CXCL6 krev   MeSH
• chemokin CXCL9 krev   MeSH
• chemokiny krev   MeSH
• kvalita života MeSH
• lidé MeSH
• rejekce štěpu krev   imunologie   MeSH
• Th1 buňky metabolismus   MeSH
• transplantace ledvin škodlivé účinky   MeSH
• Check Tag
• lidé MeSH
• Publikační typ
• časopisecké články MeSH
• Názvy látek
• chemokin CCL2 MeSH
• chemokin CCL21 MeSH
• chemokin CX3CL1 MeSH
• chemokin CXCL1 MeSH
• chemokin CXCL10 MeSH
• chemokin CXCL11 MeSH
• chemokin CXCL5 MeSH
• chemokin CXCL6 MeSH
• chemokin CXCL9 MeSH
• chemokiny MeSH
• CXCL1 protein, human MeSH Prohlížeč

Kidney allograft pathology assessment has been traditionally based on clinical and histological criteria. Despite improvements in Banff histological classification, the diagnostics in particular cases is problematic reflecting a complex pathogenesis of graft injuries. With the advent of molecular techniques, polymerase-chain reaction, oligo- and microarray technologies allowed to study molecular phenotypes of graft injuries, especially acute and chronic rejections. Moreover, development of the molecular microscope diagnostic system (MMDx) to assess kidney graft biopsies, represents the first clinical application of a microarray-based method in transplantation. Whether MMDx may replace conventional pathology is the subject of ongoing research, however this platform is particularly useful in complex histological findings and may help clinicians to guide the therapy.

• MeSH
• alografty metabolismus   MeSH
• diagnostické techniky molekulární metody   trendy   MeSH
• lidé MeSH
• přežívání štěpu fyziologie   MeSH
• rejekce štěpu diagnóza   genetika   metabolismus   MeSH
• transkriptom fyziologie   MeSH
• transplantace ledvin škodlivé účinky   trendy   MeSH
• zvířata MeSH
• Check Tag
• lidé MeSH
• zvířata MeSH
• Publikační typ
• časopisecké články MeSH
• přehledy MeSH

BACKGROUND: Monocytes represent a heterogeneous population of cells subdivided according to the expression level of membrane antigens. A pro-inflammatory (intermediate/nonclassical) subpopulation of monocytes is defined by expression of CD16. CD163 seems to be characteristically preferentially expressed by immunosuppressive monocytes. The aim of our study was to evaluate the distribution of monocyte subpopulations in 71 patients with kidney allograft transplantation. RESULTS: The phenotype was evaluated by flow cytometry in defined time points. The proportions of peripheral CD14+CD16+ monocytes were downregulated immediately after the kidney transplantation and basiliximab treatment partially attenuated this trend. The transient downregulation of the CD14+CD16+ subpopulation was adjusted to basal values in two months. The proportions of CD14+CD163+ monocytes were transiently upregulated early after the kidney transplantation and remained higher during the first month in most patients. In ATG treated patients, the expansion of CD14+CD163+ monocytes was delayed but their upregulation lasted longer. In vitro data showed the direct effect of ATG and methylprednisolone on expression of CD16 and CD163 molecules while basiliximab did not affect the phenotype of cultured monocytes. CONCLUSIONS: We assume from our data that kidney allograft transplantation is associated with modulation of monocyte subpopulations (CD14+CD16+ and CD14+CD163+) partially affected by an immunosuppressive regime used.

• MeSH
• antigen CD163 MeSH
• antigeny CD36 metabolismus   MeSH
• antigeny diferenciační B-lymfocytární metabolismus   MeSH
• antigeny diferenciační myelomonocytární metabolismus   MeSH
• CD antigeny metabolismus   MeSH
• dospělí MeSH
• fenotyp MeSH
• homologní transplantace MeSH
• imunofenotypizace MeSH
• imunosupresiva farmakologie   MeSH
• lidé středního věku MeSH
• lidé MeSH
• lipopolysacharidové receptory metabolismus   MeSH
• MHC antigeny II. třídy metabolismus   MeSH
• monocyty účinky léků   imunologie   metabolismus   MeSH
• přežívání štěpu imunologie   MeSH
• průtoková cytometrie MeSH
• receptory buněčného povrchu metabolismus   MeSH
• receptory IgG metabolismus   MeSH
• rejekce štěpu imunologie   MeSH
• senioři MeSH
• studie případů a kontrol MeSH
• transplantace ledvin * MeSH
• Check Tag
• dospělí MeSH
• lidé středního věku MeSH
• lidé MeSH
• mužské pohlaví MeSH
• senioři MeSH
• ženské pohlaví MeSH
• Publikační typ
• časopisecké články MeSH
• práce podpořená grantem MeSH
• Názvy látek
• antigen CD163 MeSH
• antigeny CD36 MeSH
• antigeny diferenciační B-lymfocytární MeSH
• antigeny diferenciační myelomonocytární MeSH
• CD antigeny MeSH
• imunosupresiva MeSH
• invariant chain MeSH Prohlížeč
• lipopolysacharidové receptory MeSH
• MHC antigeny II. třídy MeSH
• receptory buněčného povrchu MeSH
• receptory IgG MeSH

Earlier detection of antibody-mediated rejection of kidney allografts may improve graft outcomes. Profiling of gene expression holds promise for the diagnosis and prognosis of antibody-mediated rejection. Here, we identified 730 patients who received kidney transplants during 2002-2005, including 21 patients (2.9%) who experienced early acute antibody-mediated rejection. We also identified a matched group of 43 patients with early acute T cell-mediated rejection to serve as controls. Compared with patients with T cell-mediated rejection, those with antibody-mediated rejection had significantly higher intrarenal mRNA expression of the cytoprotective heme oxygenase-1 but had lower expression of the regulatory T cell marker forkhead box P3 (FoxP3), the B cell marker CD20, and the chemokine regulated upon activation, normal T cell expressed and secreted (RANTES). T cell infiltration was similar in both groups of patients. Compared with grafts that had a favorable course, those that failed as a result of antibody-mediated rejection had expression profiles suggesting a lack of regulation (less FoxP3, TGF-beta1, RANTES, and CD20). Grafts that failed as a result of T cell-mediated rejection only revealed lower expression of CD20 mRNA. In summary, these data suggest that severe antibody-mediated rejection and T cell-mediated rejection result in graft loss by distinct mechanisms. Molecular phenotypes of early acute rejection might help to identify grafts with poor prognosis, allowing earlier application of additional therapies.

• MeSH
• antigeny CD20 genetika   metabolismus   MeSH
• chemokin CCL5 genetika   metabolismus   MeSH
• dospělí MeSH
• fenotyp * MeSH
• forkhead transkripční faktory genetika   metabolismus   MeSH
• Kaplanův-Meierův odhad MeSH
• lidé středního věku MeSH
• lidé MeSH
• prediktivní hodnota testů MeSH
• prognóza MeSH
• protilátky imunologie   MeSH
• rejekce štěpu genetika   imunologie   MeSH
• retrospektivní studie MeSH
• rizikové faktory MeSH
• stanovení celkové genové exprese * MeSH
• studie případů a kontrol MeSH
• T-lymfocyty imunologie   MeSH
• transformující růstový faktor beta1 genetika   metabolismus   MeSH
• transplantace ledvin imunologie   fyziologie   MeSH
• Check Tag
• dospělí MeSH
• lidé středního věku MeSH
• lidé MeSH
• mužské pohlaví MeSH
• ženské pohlaví MeSH
• Publikační typ
• časopisecké články MeSH
• práce podpořená grantem MeSH
• Názvy látek
• antigeny CD20 MeSH
• chemokin CCL5 MeSH
• forkhead transkripční faktory MeSH
• FOXP3 protein, human MeSH Prohlížeč
• protilátky MeSH
• transformující růstový faktor beta1 MeSH