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E-GEOD-51676 - Molecular characterization of chronic antibody mediated rejection in kidney transplantation (microRNA)

Status
Released on 10 December 2015, last updated on 11 December 2015
Organism
Homo sapiens
Samples (9)
Array (1)
Protocols (5)
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.
Experiment type
transcription profiling by array 
Contacts
Anna Zito, Annarita Oranger, Antonio Lupo, Elena Ranieri, Federica Rascio, Gianluigi Zaza, Giovanni Stallone, Giuseppe Castellano, Giuseppe Grandaliano, Loreto Gesualdo, Maddalena Gigante, Margherita Gigante, Matteo Accetturo, Paola Pontrelli
Citation
A type I interferon signature characterizes chronic antibody-mediated rejection in kidney transplantation. Rascio F, Pontrelli P, Accetturo M, Oranger A, Gigante M, Castellano G, Gigante M, Zito A, Zaza G, Lupo A, Ranieri E, Stallone G, Gesualdo L, Grandaliano G. , PMID:25925804
MIAME
PlatformsProtocolsVariablesProcessedRaw
Files
Investigation descriptionE-GEOD-51676.idf.txt
Sample and data relationshipE-GEOD-51676.sdrf.txt
Raw data (1)E-GEOD-51676.raw.1.zip
Processed data (1)E-GEOD-51676.processed.1.zip
Additional data (1)E-GEOD-51676.additional.1.zip
Array designA-GEOD-16770.adf.txt
Links