Unknown,Transcriptomics,Genomics,Proteomics

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Interferon-related transcriptional program is induced by chronic hepatitis E infection in kidney-transplant recipients

ABSTRACT: Background: Hepatitis E Virus (HEV) is a new causative agent of chronic hepatitis in solid organ transplant recipients in Europe. Factors associated with the occurrence and persistence of chronic HEV infection remain largely unknown but chronic evolution seems to be the consequence of hostM-bM-^@M-^Ys immunological factors rather than of viral factors. Method: In a prospective case-control study, we have determined in whole blood of chronically HEV-infected kidney-transplant recipients the host response using microarray technology. Results: Chronically HEV-infected kidney-transplant recipients exhibited a specific transcriptional program, in which interferon effectors were prominent. The intensity of expression of each signatureM-bM-^@M-^Ys gene was significantly lower in patients who were subsequently cleared of HEV than in patients who were not. Furthermore, in patients who were cleared of HEV, a higher expression of these genes was associated with a longer delay until HEV clearance. Conclusions: The specific transcriptional program determined in chronically HEV-infected kidney-transplant recipients suggests an activation of type I interferon response. Intensity of interferon-stimulated genes expression could be useful to forecast the outcome of infection. High expression of interferon-stimulated genes could signify a dysregulation in the interferon response that might favour the persistence of the HEV infection. TrialM-bM-^@M-^Ys registration number: NCT01090232; RegistryM-bM-^@M-^Ys URL: http://clinicaltrials.gov/ct2/show/study/NCT01090232?term=kidney+transplant+recipients&cntry1=EU%3AFR&rank=2 Total RNA was extracted from whole-blood sample or monocytes of kidney-transplant patients with or without chronic hepatitis E (CHE) infection. Control patients were matched up with CHE patients for age, sex, time since kidney transplant and immunosuppressive treatment.

ORGANISM(S): Homo sapiens

SUBMITTER: Julien Textoris

PROVIDER: E-GEOD-36539 | biostudies-arrayexpress |

REPOSITORIES: biostudies-arrayexpress

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Chronic hepatitis E virus infection is specifically associated with an interferon-related transcriptional program.

Moal Valérie V Textoris Julien J Ben Amara Amira A Mehraj Vikram V Berland Yvon Y Colson Philippe P Mege Jean-Louis JL

The Journal of infectious diseases 20121016 1

<h4>Background</h4>Hepatitis E virus (HEV) is a new causative agent of chronic hepatitis in solid organ transplant recipients. Clinical studies suggest that the occurrence and persistence of chronic HEV infection are related to the immunological status of patients.<h4>Methods</h4>We used whole-genome microarray and quantitative reverse transcription polymerase chain reaction (qRT-PCR) to compare the transcriptional profiles of whole blood from 8 kidney transplant recipients with chronic HEV infe ...[more]

PMID: 23072754

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Project description:Chronic antibody-mediated rejection (CAMR) represents the main cause of kidney graft loss, but its pathogenesis is unclear. In order to uncover the molecular mechanisms underlying this condition, we characterized the molecular signature of circulating peripheral blood mononuclear cells and, separately, of CD4+ T lymphocytes isolated from CAMR patients compared to kidney transplant recipients with normal graft function and histology. In total peripheral lympho-monocytes, forty-five genes resulted differentially expressed between the two groups, most of them were up-regulated in CAMR and were involved in type I interferon signaling. In addition, in the same set of patients, 16 microRNAs resulted down-regulated in CAMR subjects compared to controls: 4 were predicted modulators of 6 mRNAs identified in the transcriptional analysis. In silico functional analysis supported the involvement of type I interferon signaling. To further confirm this hypothesis, we investigated the transcriptomic profiles of CD4+ T lymphocytes in an independent group of patients and we observed that the activation of type I interferon signaling was a specific hallmark of CAMR. In addition, in CAMR patients we detected a reduction of circulating BDCA2+ dendritic cells, the natural type I interferon- producing cells and their recruitment into the graft along with an increased expression of MXA, a type I interferon-induced protein, at tubulointerstitial and vascular level. In conclusion, our data suggest that type I interferon signaling may represent the molecular signature of CAMR. For microarray analysis, we studied 5 patients included into the control-group and 4 included into the study group. The control group was represented by renal transplant recipients undergoing protocol graft biopsies, with normal renal function and histology, in the absence of circulating anti-HLA antibodies. Study group patients showed clinical and histological evidence of CAMR according to Banff 2011 criteria.

Project description:Chronic antibody-mediated rejection (CAMR) represents the main cause of kidney graft loss, but its pathogenesis is unclear. In order to uncover the molecular mechanisms underlying this condition, we characterized the molecular signature of circulating peripheral blood mononuclear cells and, separately, of CD4+ T lymphocytes isolated from CAMR patients compared to kidney transplant recipients with normal graft function and histology. In total peripheral lympho-monocytes, forty-five genes resulted differentially expressed between the two groups, most of them were up-regulated in CAMR and were involved in type I interferon signaling. In addition, in the same set of patients, 16 microRNAs resulted down-regulated in CAMR subjects compared to controls: 4 were predicted modulators of 6 mRNAs identified in the transcriptional analysis. In silico functional analysis supported the involvement of type I interferon signaling. To further confirm this hypothesis, we investigated the transcriptomic profiles of CD4+ T lymphocytes in an independent group of patients and we observed that the activation of type I interferon signaling was a specific hallmark of CAMR. In addition, in CAMR patients we detected a reduction of circulating BDCA2+ dendritic cells, the natural type I interferon- producing cells and their recruitment into the graft along with an increased expression of MXA, a type I interferon-induced protein, at tubulointerstitial and vascular level. In conclusion, our data suggest that type I interferon signaling may represent the molecular signature of CAMR. For microarray analysis, we studied 8 patients included into the control-group and 10 included into the study group. The control group was represented by renal transplant recipients undergoing protocol graft biopsies, with normal renal function and histology, in the absence of circulating anti-HLA antibodies. Study group patients showed clinical and histological evidence of CAMR according to Banff 2011 criteria.

Project description:Chronic antibody-mediated rejection (CAMR) represents the main cause of kidney graft loss, but its pathogenesis is unclear. In order to uncover the molecular mechanisms underlying this condition, we characterized the molecular signature of circulating peripheral blood mononuclear cells and, separately, of CD4+ T lymphocytes isolated from CAMR patients compared to kidney transplant recipients with normal graft function and histology. In total peripheral lympho-monocytes, forty-five genes resulted differentially expressed between the two groups, most of them were up-regulated in CAMR and were involved in type I interferon signaling. In addition, in the same set of patients, 16 microRNAs resulted down-regulated in CAMR subjects compared to controls: 4 were predicted modulators of 6 mRNAs identified in the transcriptional analysis. In silico functional analysis supported the involvement of type I interferon signaling. To further confirm this hypothesis, we investigated the transcriptomic profiles of CD4+ T lymphocytes in an independent group of patients and we observed that the activation of type I interferon signaling was a specific hallmark of CAMR. In addition, in CAMR patients we detected a reduction of circulating BDCA2+ dendritic cells, the natural type I interferon- producing cells and their recruitment into the graft along with an increased expression of MXA, a type I interferon-induced protein, at tubulointerstitial and vascular level. In conclusion, our data suggest that type I interferon signaling may represent the molecular signature of CAMR. We performed microarray experiments in CD4+ T cells isolated from a small independent group of 5 patients included into the control-group and 5 included into the study group. The control group was represented by renal transplant recipients undergoing protocol graft biopsies, with normal renal function and histology, in the absence of circulating anti-HLA antibodies. Study group patients showed clinical and histological evidence of CAMR according to Banff 2011 criteria.

Dataset Information

Interferon-related transcriptional program is induced by chronic hepatitis E infection in kidney-transplant recipients

Publications

Chronic hepatitis E virus infection is specifically associated with an interferon-related transcriptional program.

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