Heart transplant biopsies-second test set
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ABSTRACT:
ORGANISM(S): Homo sapiens
PROVIDER: GSE4470 | GEO | 2006/03/15
SECONDARY ACCESSION(S): PRJNA94541
REPOSITORIES: GEO
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Project description:MOLECULAR PROFILING IMPROVES DIAGNOSES OF REJECTION AND INFECTION IN TRANSPLANTED ORGANS. The monitoring of transplanted hearts is currently based on histological evaluation of endomyocardial biopsies, a method that is fairly insensitive and that does not always accurately discriminate between rejection and infection in the heart. Accurate diagnosis of rejection and infection is absolutely crucial, however, as the respective treatments are completely different. Using microarrays we analyzed gene expression in 76 cardiac biopsies from 40 heart recipients undergoing rejection, no rejection, or T. cruzi infection. We found a set of 98 genes whose expression patterns were typical of acute rejection, and 87 genes that discriminated between rejection and T. cruzi infection. These sets revealed acute rejection episodes up to two weeks earlier, and trypanosome infection up to two months earlier than did histological evaluation. When applied to raw data from other institutions, the two sets of predictive genes were also able to accurately pinpoint acute rejection of lung and kidney transplants, as well as bacterial infections in kidneys. In addition to their usefulness as diagnostic tools, the data suggest that there are similarities in the biology of the processes involved in rejection of different grafts and also in the tissue responses to pathogens as diverse as bacteria and protozoa. pre-rejection: GSM47949, GSM48048, GSM49625 non-rejection: GSM47957, GSM48045, GSM48049, GSM48057, GSM48072, GSM48089, GSM48092, GSM49624, GSM49654, GSM49656, GSM49657, GSM49658, GSM49661, GSM49666, GSM49748, GSM49750, GSM49751, GSM49752, GSM49754, GSM49756, GSM49757, GSM49758, GSM49762, GSM49765, GSM49766, GSM49767, GSM49769, GSM49771, GSM49773, GSM49774, GSM49781, GSM49782, GSM49783, GSM49784 acute rejection: GSM48040, GSM48043, GSM48046, GSM48047, GSM48050, GSM48053, GSM48056, GSM49655, GSM49747, GSM49749, GSM49755, GSM49759, GSM49761, GSM49763, GSM49764, GSM49780 pre-Chagas disease reactivation: GSM48089, GSM49756, GSM49757, GSM49758, GSM49767, GSM49769, GSM49771 Chagas disease reactivation: GSM49753, GSM49760, GSM49768, GSM49772, GSM49775, GSM49776, GSM49777, GSM49778 Toxoplasma myocarditis: GSM48058 first subset ("summer"): GSM47949, GSM47957, GSM48040, GSM48043, GSM48045, GSM48046, GSM48047, GSM48048, GSM48049, GSM48050, GSM48053, GSM48056, GSM48057, GSM48058, GSM48072, GSM48089, GSM48092, GSM49624, GSM49625, GSM49654, GSM49655, GSM49656, GSM49657, GSM49658, GSM49661, GSM49666, GSM49747, GSM49748, GSM49749, GSM49750, GSM49751, GSM49752 second subset ("winter"): GSM49753, GSM49754, GSM49755, GSM49756, GSM49757, GSM49758, GSM49759, GSM49760, GSM49761, GSM49762, GSM49763, GSM49764, GSM49765, GSM49766, GSM49767, GSM49768, GSM49769, GSM49770, GSM49771, GSM49772, GSM49773, GSM49774, GSM49775, GSM49776, GSM49777, GSM49778, GSM49780, GSM49781, GSM49782, GSM49783, GSM49784 Keywords = cardiac transplant Keywords = acute rejection Keywords = infection Keywords: repeat sample
2005-10-24 | GSE2596 | GEO
Project description:Histological features of acute rejection can be detected in surveillance biopsies despite stable graft function and can negatively impact graft outcomes. However, routine surveillance biopsies for detection of subclinical rejection are not generally performed due to potential risks and costs associated with repeated biopsies. Noninvasive biomarkers are required to facilitate early detection of acute rejection and borderline changes. We examined the impact of histological abnormalities at 3-month in surveillance biopsies on graft outcomes in kidney transplant recipients from the prospective Genomics of Chronic Allograft Rejection (GoCAR) study. We then performed RNA sequencing on whole blood collected at the time of biopsy in 88 patients (22 vs. 66) to identify transcripts associated with histological abnormalities. Subjects with subclinical ACR or borderline ACR at 3 month (ACR-3) had higher risk of subsequent clinical acute rejection at 12 and 24 month (P < 0.05), more rapid functional decline (P < 0.05) and a decreased graft survival in adjusted cox analysis (P < 0.01) than patients with no abnormalities on 3-month biopsy. We then identified a 17-gene signature in peripheral blood that accurately diagnosed ACR-3.
2019-09-11 | GSE120396 | GEO
Project description:Histological features of acute rejection can be detected in surveillance biopsies despite stable graft function and can negatively impact graft outcomes. However, routine surveillance biopsies for detection of subclinical rejection are not generally performed due to potential risks and costs associated with repeated biopsies. Noninvasive biomarkers are required to facilitate early detection of acute rejection and borderline changes. We examined the impact of histological abnormalities at 3-month in surveillance biopsies on graft outcomes in kidney transplant recipients from the prospective Genomics of Chronic Allograft Rejection (GoCAR) study. We then performed RNA sequencing on whole blood collected at the time of biopsy in 88 patients (22 vs. 66) to identify transcripts associated with histological abnormalities. Subjects with subclinical ACR or borderline ACR at 3 month (ACR-3) had higher risk of subsequent clinical acute rejection at 12 and 24 month (P < 0.05), more rapid functional decline (P < 0.05) and a decreased graft survival in adjusted cox analysis (P < 0.01) than patients with no abnormalities on 3-month biopsy. We then identified a 17-gene signature in peripheral blood that accurately diagnosed ACR-3. The gene set was then validated for diagnosis of ACR-3 using microarray data (N=65; 12 vs. 53; 26 overlapping with the RNAseq cohort).
2019-09-11 | GSE120397 | GEO
Project description:CONTEXT Slowly progressive chronic tubulo-interstitial damage jeopardizes long-term renal allograft survival. Both immune and non-immune mechanisms are thought to contribute, but the most promising targets for timely intervention have not been identified. OBJECTIVE In the current study we seek to determine the driving force behind progressive histological damage of renal allografts, without the interference of donor pathology, delayed graft function and acute graft rejection. DESIGN We used microarrays to examine whole genome expression profiles in renal allograft protocol biopsies, and analyzed the correlation between gene expression and the histological appearance over time. The gene expression profiles in these protocol biopsies were then compared with gene expression of biopsies with acute T-cell mediated rejection. PATIENTS Human renal allograft biopsies (N=120) were included: 96 rejection-free protocol biopsies and 24 biopsies with T-cell mediated acute rejection. RESULTS In this highly cross-validated study, we demonstrate the significant association of established, ongoing and future chronic histological damage with regulation of adaptive immune gene expression (T-cell and B-cell transcript sets) and innate immune response gene expression (dendritic cell, NK-cell, mast cell and granulocyte transcripts). We demonstrate the ability of gene expression analysis to perform as a quantitative marker for ongoing inflammation with a wide dynamic range: from subtle subhistological inflammation prior to development of chronic damage, over moderate subclinical inflammation associated with chronic histological damage, to marked inflammation of Banff-grade acute T-cell mediated rejection. CONCLUSION Progressive chronic histological damage after kidney transplantation is associated with significant regulation of both innate and adaptive immune responses, months before the histological lesions appear. This study therefore corroborates the hypothesis that quantitative inflammation below the diagnostic threshold of classic T-cell or antibody-mediated rejection is associated with early subclinical stages of progressive renal allograft damage. We used microarrays to examine whole genome expression profiles in renal allograft protocol biopsies, and analyzed the correlation between gene expression and the histological appearance over time. The gene expression profiles in these protocol biopsies were then compared with gene expression of biopsies with acute T-cell mediated rejection. Human renal allograft biopsies (N=120) were included: 96 rejection-free protocol biopsies and 24 biopsies with T-cell mediated acute rejection.
2011-12-10 | E-GEOD-25902 | biostudies-arrayexpress
Project description:CONTEXT Slowly progressive chronic tubulo-interstitial damage jeopardizes long-term renal allograft survival. Both immune and non-immune mechanisms are thought to contribute, but the most promising targets for timely intervention have not been identified. OBJECTIVE In the current study we seek to determine the driving force behind progressive histological damage of renal allografts, without the interference of donor pathology, delayed graft function and acute graft rejection. DESIGN We used microarrays to examine whole genome expression profiles in renal allograft protocol biopsies, and analyzed the correlation between gene expression and the histological appearance over time. The gene expression profiles in these protocol biopsies were then compared with gene expression of biopsies with acute T-cell mediated rejection. PATIENTS Human renal allograft biopsies (N=120) were included: 96 rejection-free protocol biopsies and 24 biopsies with T-cell mediated acute rejection. RESULTS In this highly cross-validated study, we demonstrate the significant association of established, ongoing and future chronic histological damage with regulation of adaptive immune gene expression (T-cell and B-cell transcript sets) and innate immune response gene expression (dendritic cell, NK-cell, mast cell and granulocyte transcripts). We demonstrate the ability of gene expression analysis to perform as a quantitative marker for ongoing inflammation with a wide dynamic range: from subtle subhistological inflammation prior to development of chronic damage, over moderate subclinical inflammation associated with chronic histological damage, to marked inflammation of Banff-grade acute T-cell mediated rejection. CONCLUSION Progressive chronic histological damage after kidney transplantation is associated with significant regulation of both innate and adaptive immune responses, months before the histological lesions appear. This study therefore corroborates the hypothesis that quantitative inflammation below the diagnostic threshold of classic T-cell or antibody-mediated rejection is associated with early subclinical stages of progressive renal allograft damage.
2011-12-10 | GSE25902 | GEO
Project description:18 zero-hour and 18 selected post-transplant (Tx) biopsy samples from 18 kidney allografts (8 acute kidney injury (AKI), 10 PBx - protocol biopsies - controls) were analyzed by using the Affymetrix GeneChipM-BM-. miRNA 3.0 Array. Comparison between control group (protocol biopsies) and indication biopsies with histological lesions of acute tubular necrosis without rejection (ATN).
2015-01-15 | E-GEOD-53771 | biostudies-arrayexpress
Project description:18 zero-hour and 18 selected post-transplant (Tx) biopsy samples from 18 kidney allografts (8 acute kidney injury (AKI), 10 PBx - protocol biopsies - controls) were analyzed by using the Affymetrix GeneChip® Human Gene 2.0 ST Array. comparison between control group (protocol biopsies) and indication biopsies with histological lesions of acute tubular necrosis without rejection (ATN)
2015-01-15 | E-GEOD-53769 | biostudies-arrayexpress
Project description:Aims. Serial invasive endomyocardial biopsies (EMB) remain the gold standard for acute cellular rejection (ACR) diagnosis. However histological grading has several limitations. We aimed to explore the value of myocardial Gene Expression Profiling (GEP) for diagnosing and identifying predictive biomarkers of ACR. Methods. A case-control study nested within a retrospective heart transplant patients cohort included 126 patients with median (IQR) age 50 (41-57) years and 111 (88%) males. Among 1157 EMB performed, 467 were eligible (i.e, corresponding to either ISHLT grade 0 or â¥3A), among which 36 were selected for GEP according to the grading: 0 (CISHLT, n= 13); rejection â¥3A (RISHLT, n=13); 0 one month before ACR (BRISHLT, n=10). Results. We found 294 genes differentially expressed between CISHLT and RISHLT, mainly involved in immune activation, and inflammation. Hierarchical clustering showed a clear segregation of CISHLT and RISHLT groups and heterogeneity of GEP within RISHLT. All EMB presented immune activation, but some RISHLT EMB were strongly subject to inflammation, whereas others, closer to CISHLT, were characterized by structural modifications with lower inflammation level. We identified 15 probes significantly different between BRISHLT and CISHLT, including the gene of the muscular protein TTN. This result suggests that structural alterations precede inflammation in ACR. Linear Discriminant Analysis based on these 15 probes was able to identify the histological status of every 36 samples. Conclusion. Myocardial GEP is a helpful method to accurately diagnose ACR, and predicts rejection one month before its histological occurrence. These results should be considered in cardiac allograft recipientsâ care.
2017-03-07 | E-MTAB-5136 | biostudies-arrayexpress
Project description:Endomyocardial biopsies with different acute rejection gradings
| PRJNA103085 | ENA
Project description:Liver transplantation is the only lifesaving therapy for patients with irreversible liver failure, and 30% of the recipients experience acute rejection in the first 12 months following transplantation. Acute rejection is diagnosed by core needle biopsy and noninvasive methods for predicting acute rejection could improve clinical care. MicroRNAs (miRNAs) are emerging as biomarkers of clinically significant events. We investigated whether circulating extracellular miRNA profiles in sera matched to liver allograft biopsies predict human liver allograft status. Small RNA sequencing and TaqMan low-density array analysis of RNA from biopsy matched sera identified that liver specific miR-122, and miRs -885, -210, -194, 193b, -192, -148a, -34a and -22 distinguish patients with acute rejection biopsies from those with biopsies without rejection features (false discovery rate of <0.15). We measured absolute levels of these informative 9 miRNAs using quantitative real-time PCR assays. Receiver-operating-characteristic (ROC) curve analysis of circulating levels of miRNA levels validated that all 9 miRNAs discriminate patients with acute rejection in their biopsies from those without rejection in their biopsies (P <0.01 to P<0.0001). A parsimonious diagnostic signature of miR-122 and miR-194 was diagnostic of acute rejection with a sensitivity of 79% (95% confidence interval [CI], 49% to 95%) and a specificity of 88% (95% CI, 64% to 99%) (area under the curve, 0.91; 95% CI, 0.81 to 1.00; P<0.001 by ROC curve analysis). Our findings suggest that a molecular signature of miR-122 and miR-194 in serum offers a noninvasive means of diagnosing acute rejection including mild forms in human liver allografts.
2019-06-30 | GSE69579 | GEO