title: IL28B genetic variation and cytomegalovirus-specific T-cell immunity in allogeneic stem cell transplant recipients.
abstract: A single nucleotide polymorphism (SNP), 3 kbp upstream of the IL28B gene (rs12979860; C/T), has been shown to influence the dynamics of cytomegalovirus (CMV) replication in allogeneic stem cell transplant recipients (Allo-SCT). We investigated whether this SNP had any effect on the dynamics of CMV-specific T-cell immunity in these patients. CMV pp65/IE-1 IFN-γ CD8+and CD4+T cells were enumerated by flow cytometry in 85 patients with no prior CMV DNAemia (group A) and in 57 after the onset of CMV DNAemia (group B). Donor IL28B genotype was determined by real-time PCR and plasma levels of IL-28B were quantitated by ELISA. CMV-specific T-cell counts and plasma IL-28B levels in patients in group A were not significantly different among the IL28B genotype groups. Patients harboring the donor IL28B T/T genotype appeared to expand CMV-specific IFN-γ CD8+cells to a higher level in response to viral replication than their C/T and C/C counterparts. Fewer patients in the T/T group received pre-emptive antiviral therapy (P = 0.05). Overall, a significant inverse correlation was observed between median IL-28B levels measured prior to the CMV DNAemia onset and the level of CMV-specific CD8+T cells enumerated after detection of CMV DNAemia (σ = -0.471; P = 0.013). In summary, the data suggested that the protective effect attributed to the rs12979860 SNP minor T allele could be mediated, at least in part, by eliciting robust CMV-specific T-cell responses. J. Med. Virol. 89:685-695, 2017. © 2016 Wiley Periodicals, Inc.
authors: Microbiology Service, Hospital Clínico Universitario, Fundación de Investigación INCLIVA, Valencia, Spain.
authors: Isabel
authors: I
authors: Corrales
authors: Hematology and Medical Oncology Service, Hospital Clínico Universitario, Fundación de Investigación INCLIVA, Valencia, Spain.|Department of Medicine, School of Medicine, University of Valencia, Valencia, Spain.
authors: Carlos
authors: C
authors: Solano
authors: Hematology and Medical Oncology Service, Hospital Clínico Universitario, Fundación de Investigación INCLIVA, Valencia, Spain.
authors: Paula
authors: P
authors: Amat
authors: Microbiology Service, Hospital Clínico Universitario, Fundación de Investigación INCLIVA, Valencia, Spain.
authors: Estela
authors: E
authors: Giménez
authors: Hematology Service, Hospital de la Princesa, Madrid, Spain.
authors: Rafael
authors: R
authors: de la Cámara
authors: Hematology Service, Hospital Morales Meseguer, Murcia, Spain.
authors: José
authors: J
authors: Nieto
authors: Hematology Service, Hospital Ramón y Cajal, Madrid, Spain.
authors: Javier
authors: J
authors: López
authors: Hematology Service, Hospital de la Princesa, Madrid, Spain.
authors: Ana
authors: A
authors: García-Noblejas
authors: Hematology and Medical Oncology Service, Hospital Clínico Universitario, Fundación de Investigación INCLIVA, Valencia, Spain.
authors: José Luis
authors: JL
authors: Piñana
authors: Microbiology Service, Hospital Clínico Universitario, Fundación de Investigación INCLIVA, Valencia, Spain.|Department of Microbiology, School of Medicine, University of Valencia, Valencia, Spain.
authors: David
authors: D
authors: Navarro
mesh_terms: D000293:Adolescent; D000328:Adult; D000368:Aged; D003587:Cytomegalovirus / Q000276:immunology*; D004797:Enzyme-Linked Immunosorbent Assay; D005260:Female; D005434:Flow Cytometry; D060005:Genotyping Techniques; D006801:Humans; D007371:Interferon-gamma / Q000032:analysis; D007372:Interferons; D007378:Interleukins / Q000097:blood / Q000235:genetics*; D008297:Male; D008875:Middle Aged; D020641:Polymorphism, Single Nucleotide; D060888:Real-Time Polymerase Chain Reaction; D012189:Retrospective Studies; D033581:Stem Cell Transplantation; D013601:T-Lymphocytes / Q000276:immunology*; D066027:Transplant Recipients; D014184:Transplantation, Homologous; D055815:Young Adult; D000095022:Interferon Lambda
chemical_list: D007371:Interferon-gamma; D007372:Interferons; D007378:Interleukins; C000624353:interferon-lambda, human; D000095022:Interferon Lambda
keywords: CMV DNAemia; IFN λ3; IL28B gene polymorphisms; T-cell immunity; allogeneic stem cell transplantation; cytomegalovirus