title: Inherent transcriptional signatures of NK cells are associated with response to IFNα + rivabirin therapy in patients with Hepatitis C Virus.
abstract: BACKGROUND
  Differences in the expression of Natural Killer cell receptors have been reported to reflect divergent clinical courses in patients with chronic infections or tumors. However, extensive molecular characterization at the transcriptional level to support this view is lacking. The aim of this work was to characterize baseline differences in purified NK cell transcriptional activity stratified by response to treatment with PEG-IFNα/RBV in patients chronically infected with HCV.
  
  
  METHODS
  To this end we here studied by flow cytometer and gene expression profile, phenotypic and transcriptional characteristics of purified NK cells in patients chronically infected with HCV genotype-1 virus who were subsequently treated with PEG-IFNα/RBV. Results were further correlated with divergent clinical response obtained after treatment.
  
  
  RESULTS
  The pre-treatment transcriptional patterns of purified NK cells from patients subsequently undergoing a sustained virologic response (SVR) clearly segregated from those of non-responder (NR) patients. A set of 476 transcripts, including molecules involved in RNA processing, ubiquitination pathways as well as HLA class II signalling were differently expressed among divergent patients. In addition, treatment outcome was associated with differences in surface expression of NKp30 and NKG2D. A complex relationship was observed that suggested for extensive post-transcriptional editing. Only a small number of the NK cell transcripts identified were correlated with chronic HCV infection/replication indicating that inherent transcriptional activity prevails over environment effects such as viral infection.
  
  
  CONCLUSIONS
  Collectively, inherent/genetic modulation of NK cell transcription is involved in setting the path to divergent treatment outcomes and could become useful to therapeutic advantage.
authors: Maria Libera
authors: ML
authors: Ascierto
authors: Federica
authors: F
authors: Bozzano
authors: Davide
authors: D
authors: Bedognetti
authors: Francesco
authors: F
authors: Marras
authors: Cathy
authors: C
authors: Schechterly
authors: Kentaro
authors: K
authors: Matsuura
authors: Antonino
authors: A
authors: Picciotto
authors: Simona
authors: S
authors: Marenco
authors: Yingdong
authors: Y
authors: Zhao
authors: Valeria
authors: V
authors: DeGiorgi
authors: Michele
authors: M
authors: Sommariva
authors: Lorenzo
authors: L
authors: Moretta
authors: Ena
authors: E
authors: Wang
authors: Harvey J
authors: HJ
authors: Alter
authors: Francesco M
authors: FM
authors: Marincola
authors: Andrea
authors: A
authors: De Maria
mesh_terms: D015331:Cohort Studies; D020869:Gene Expression Profiling; D016174:Hepacivirus / Q000187:drug effects*; D019698:Hepatitis C, Chronic / Q000188:drug therapy* / Q000235:genetics*; D006801:Humans; D016898:Interferon-alpha / Q000494:pharmacology / Q000627:therapeutic use*; D007372:Interferons; D007378:Interleukins / Q000235:genetics; D007694:Killer Cells, Natural / Q000187:drug effects / Q000378:metabolism*; D055655:NK Cell Lectin-Like Receptor Subfamily K / Q000378:metabolism; D055628:Natural Cytotoxicity Triggering Receptor 3 / Q000378:metabolism; D020641:Polymorphism, Single Nucleotide / Q000235:genetics; D015203:Reproducibility of Results; D012254:Ribavirin / Q000494:pharmacology / Q000627:therapeutic use*; D014158:Transcription, Genetic / Q000187:drug effects*; D016896:Treatment Outcome; D000095022:Interferon Lambda
chemical_list: D016898:Interferon-alpha; D007372:Interferons; D007378:Interleukins; D055655:NK Cell Lectin-Like Receptor Subfamily K; D055628:Natural Cytotoxicity Triggering Receptor 3; D012254:Ribavirin; C000624353:interferon-lambda, human; D000095022:Interferon Lambda