Circulating small RNAs in transplant glomerulopathy
Ontology highlight
ABSTRACT:
ORGANISM(S): Homo sapiens
PROVIDER: GSE156874 | GEO | 2021/06/30
REPOSITORIES: GEO
Similar Datasets
Project description:Circulating small RNAs in transplant glomerulopathy
| PRJNA659355 | ENA
Project description:We investigated the clinical, histopathologic and genomic features of donor-specific antibody (DSA) +/C4d- and DSA-/C4d- transplant glomerulopathy (TGP) using microarrays. Comparison of the gene expression profiles of DSA-/C4d- TGP biopsies with ptc+g score > 1 to normal and IFTA (Interstitial Fibrosis and Tubular Atrophy) biopsies by microarrays revealed increased expression of quantitative cytotoxic T cell--associated transcripts (QCAT). However, CAMR (chronic antibody-mediated rejection) and DSA+/C4d- TGP had increased expression of QCAT, interferon-gamma and rejection induced, constitutive macrophage-associated, natural killer cell-associated, and DSA selective transcripts. B cell and endothelial cell associated transcripts expression were upregulated only in CAMR biopsies. Our results suggest that while DSA+/C4d- TGP should be classified under CAMR, DSA-/C4d- TGP with ptc+g score > 1 probably develops through a chronic cellular immune response. Total of 57 arrays included in this study. G1. Normal transplant kidney biopsies (N= 12); G2. Non-specific IFTA (N= 17); G3. TGP DSA-/C4d- (N=8); G4. TGP DSA+/C4d- (N= 9); G5. CAMR/TGP C4d+/DSA+ (N= 11)
2013-02-07 | E-GEOD-44131 | biostudies-arrayexpress
Project description:We investigated the clinical, histopathologic and genomic features of donor-specific antibody (DSA) +/C4d- and DSA-/C4d- transplant glomerulopathy (TGP) using microarrays. Comparison of the gene expression profiles of DSA-/C4d- TGP biopsies with ptc+g score > 1 to normal and IFTA (Interstitial Fibrosis and Tubular Atrophy) biopsies by microarrays revealed increased expression of quantitative cytotoxic T cell--associated transcripts (QCAT). However, CAMR (chronic antibody-mediated rejection) and DSA+/C4d- TGP had increased expression of QCAT, interferon-gamma and rejection induced, constitutive macrophage-associated, natural killer cell-associated, and DSA selective transcripts. B cell and endothelial cell associated transcripts expression were upregulated only in CAMR biopsies. Our results suggest that while DSA+/C4d- TGP should be classified under CAMR, DSA-/C4d- TGP with ptc+g score > 1 probably develops through a chronic cellular immune response.
2013-02-07 | GSE44131 | GEO
Project description:Transplant glomerulopathy (TGP) is frequently found in the setting of chronic antibody mediated rejection along with microvascular inflammation (MVI) (peritubular capillaritis+glomerulitis score > 1) and/or positive c4d staining. We assessed the molecular profiles of TGP in the absence of microvascular inflammation and C4d staining as compared to TGP with positive MVI and/or C4d. Gene expression profiles of TGP in the absence of microvascular inflammation and C4d lack molecular features of antibody-mediated rejection but suggest chronic cellular rejection.
2017-01-17 | GSE93659 | GEO
Project description:We studied intragraft gene expression profiles of positive crossmatch (+XM) kidney transplant recipients who develop transplant glomerulopathy (TG) and those who do not. Whole genome microarray analysis and quantitative rt-PCR for 30 transcripts were performed on RNA from protocol renal allograft biopsies in 3 groups: 1) +XM/TG+ biopsies before and after TG; 2) +XM/NoTG; and 3) negative crossmatch kidney transplants (control). Microarray comparisons showed few differentially expressed genes between paired biopsies from +XM/TG+ recipients before and after the diagnosis of TG. Comparing +XM/TG+ and control groups, significantly altered expression was seen for 2,447 genes (18%) and 3,200 genes (24%) at early and late time points, respectively. Canonical pathway analyses of differentially expressed genes showed inflammatory genes associated with innate and adaptive immune responses. Comparing +XM/TG+ and +XM/NoTG groups, 3,718 probe sets were differentially expressed but these were over-represented in only 4 pathways. A classic accommodation phenotype was not identified. Using rt-PCR, the expression of inflammatory genes was significantly increased in +XM/TG+ recipients compared to control biopsies and to +XM/NoTG biopsies. In conclusion, pre-transplant DSA results in a gene expression profile characterized by inflammation and cellular infiltration and the majority of XM+ grafts are exposed to chronic injury. We analyzed gene expression from 2 groups of positive crossmatch kidney transplant recipients (+XM/TG+ and +XM/TG-). Patients in the +XM/TG+ group had 2 biopsies - prior to the development of transplant glomerulopathy on biopsy (Biopsy 1; cg=0; n=10) and after development of transplant glomerulopathy (Biopsy 2; cg>0; n=10). The +XM/TG- patients had only a Biopsy 2 (cg=0; n=11). A third patient group served as controls (n=10) and were from -XM recipients. This dataset is part of the TransQST collection.
2012-05-30 | E-GEOD-34748 | biostudies-arrayexpress
Project description:Kidney transplant biopsies showing transplant glomerulopathy (cg > 0) and microvascular inflammation (MVI) in the absence of C4d staining and DSAs do not fulfill the criteria for chronic active antibody-mediated rejection (CA-AMR) diagnosis or any other Banff category. In this multicenter intercontinental study including 36 cases, we compared, among other types of data, the transcriptomic profiles of 14 KTx biopsies classified as cg+MVI DSA-/C4d- with 22 classified as CA-AMR DSA+/C4d+ through novel transcriptomic analysis using the NanoString B-HOT panel. Due to lack of tissue, one sample was excluded from the transcriptomic analysis. In our analysis, nineteen genes were differentially expressed between the two study groups. Samples diagnosed with CA-AMR DSA+/C4d+ showed a higher transcriptomic cell type scores for macrophages in an environment characterized by increased expression of complement-related genes (i.e., C5AR1) and higher activity of angiogenesis, IFTA, CA-AMR, and DSA-related pathways when compared to samples diagnosed with cg+MVI DSA-/C4d-. Samples diagnosed with cg+MVI DSA-/C4d- displayed a higher activity of the T-cell receptor and B-cell associated transcripts. These results were coherent with those from our 5-plex immunofluorescence orthogonal analyses showing higher abundance of innate immune cells in the interstitium of CA-AMR DSA+/C4d+ samples when compared to cg+MVI DSA-/C4d- samples and a higher glomerular abundance of pan-T-cells in cg+MVI DSA-/C4d- samples when compared to CA-AMR DSA+/C4d+ samples. Here we show that using novel multiomic techniques, KTx biopsies with cg+MVI DSA-/C4d- have a prominent T-cell presence and activity, putting forward the possibility that these represent a more T-cell-dominant phenotype.
2023-10-09 | GSE242984 | GEO
Project description:We studied intragraft gene expression profiles of positive crossmatch (+XM) kidney transplant recipients who develop transplant glomerulopathy (TG) and those who do not. Whole genome microarray analysis and quantitative rt-PCR for 30 transcripts were performed on RNA from protocol renal allograft biopsies in 3 groups: 1) +XM/TG+ biopsies before and after TG; 2) +XM/NoTG; and 3) negative crossmatch kidney transplants (control). Microarray comparisons showed few differentially expressed genes between paired biopsies from +XM/TG+ recipients before and after the diagnosis of TG. Comparing +XM/TG+ and control groups, significantly altered expression was seen for 2,447 genes (18%) and 3,200 genes (24%) at early and late time points, respectively. Canonical pathway analyses of differentially expressed genes showed inflammatory genes associated with innate and adaptive immune responses. Comparing +XM/TG+ and +XM/NoTG groups, 3,718 probe sets were differentially expressed but these were over-represented in only 4 pathways. A classic accommodation phenotype was not identified. Using rt-PCR, the expression of inflammatory genes was significantly increased in +XM/TG+ recipients compared to control biopsies and to +XM/NoTG biopsies. In conclusion, pre-transplant DSA results in a gene expression profile characterized by inflammation and cellular infiltration and the majority of XM+ grafts are exposed to chronic injury.
2012-05-30 | GSE34748 | GEO
Project description:This pilot phase II trial studies how well giving donor T cells after donor stem cell transplant works in treating patients with hematologic malignancies. In a donor stem cell transplant, the donated stem cells may replace the patient’s immune cells and help destroy any remaining cancer cells (graft-versus-tumor effect). Giving an infusion of the donor’s T cells (donor lymphocyte infusion) after the transplant may help increase this effect.
| 2143763 | ecrin-mdr-crc
Project description:Experiments in preclinical transplant models have indicated that preoperative administration of donor-derived M regs to transplant recipients may promote beneficial regulatory responses to a subsequent allograft. This contention is supported by results from the TAIC-I and –II clinical studies, which demonstrated that infusion of a crude cell preparation containing regulatory macrophages was both safe and could promote a state of donor-specific hyporesponsiveness. In an extension of this work, two patients were treated with donor-derived M regs prior to receiving a living-donor kidney transplant. Keywords: Classification of clinical samples
2011-11-28 | GSE24172 | GEO
Project description:Transplant glomerulopathy develops through multiple mechanisms, including donor-specific antibodies, T cells and innate immunity. This study investigates circulating small RNA profiles in serum samples of kidney transplant recipients with biopsy-proven transplant glomerulopathy. Among total small RNA population, miRNAs were the most abundant species in the serum of kidney transplant patients. In addition, fragments arising from mature tRNA and rRNA were detected. Most of the tRNA fragments were generated from 5' ends of mature tRNA and mainly from two parental tRNAs: tRNA-Gly and tRNA-Glu. Moreover, transplant patients with transplant glomerulopathy displayed a novel tRNA fragments signature. Gene expression analysis from allograft tissues demonstrated changes in canonical pathways related to immune activation such as iCos-iCosL signaling pathway in T helper cells, Th1 and Th2 activation pathway, and dendritic cell maturation. mRNA targets of down-regulated miRNAs such as miR-1224-5p, miR-4508, miR-320, miR-378a from serum were globally upregulated in tissue. Integration of serum miRNA profiles with tissue gene expression showed that changes in serum miRNAs support the role of T-cell mediated mechanisms in ongoing allograft injury.
| S-EPMC8226568 | biostudies-literature