title: Low Interferon Relative-Response to Cytomegalovirus Is Associated with Low Likelihood of Intrauterine Transmission of the Virus.
abstract: BACKGROUND
  Congenital Cytomegalovirus (CMV) is a very common intrauterine infection which can cause severe mental and hearing impairments. Notably, only 40% of primarily infected women transmit CMV to the fetus. CMV-specific T-cell response has a role in CMV disease but individual immune heterogeneity precludes reliable correlation between measurable T-cells response and intrauterine transmission.
  
  
  OBJECTIVE
  To establish a correlation between maternal T-cells response and fetal CMV transmission using an individual normalized immune response.
  
  
  METHODS
  We analyzed IFN-γ secretion upon whole blood stimulation from primary CMV-infected pregnant women, with either CMV-peptides or PHA-mitogen.
  
  
  RESULTS
  We established a new normalization method of individual IFN-γ response to CMV by defining the ratio between specific-CMV response and non-specific mitogen response (defined as IFN-γ relative response, RR), aiming to overcome high person-to-person immune variability. We found a unique subpopulation of women with low IFN-γ RR strongly correlated with absence of transmission. IFN-γ RR lower than 1.8% (threshold determined by ROC analysis) reduces the pre-test probability of transmission from 40% to 8%, revealing an unexpected link between low IFN-γ RR and non-transmission.
  
  
  CONCLUSIONS
  In pregnant women with primary CMV infection, low IFN-γ RR is associated with low risk of transmission.
authors.affiliation: Research Laboratory of Infectious Diseases, Shaare Zedek Medical Center, affiliated to the Hebrew University Medical School, Jerusalem, Israel.
authors.forename: Yifat
authors.initials: Y
authors.lastname: Eldar-Yedidia
authors.affiliation: Department of Pediatrics, Shaare Zedek Medical Center, Jerusalem, Israel.
authors.forename: Maskit
authors.initials: M
authors.lastname: Bar-Meir
authors.affiliation: Research Laboratory of Infectious Diseases, Shaare Zedek Medical Center, affiliated to the Hebrew University Medical School, Jerusalem, Israel.
authors.forename: Miriam
authors.initials: M
authors.lastname: Hillel
authors.affiliation: Research Laboratory of Infectious Diseases, Shaare Zedek Medical Center, affiliated to the Hebrew University Medical School, Jerusalem, Israel.
authors.forename: Guila
authors.initials: G
authors.lastname: Abitbol
authors.affiliation: Microbiology @ Immunology laboratories, Shaare Zedek Medical Center, Jerusalem, Israel.
authors.forename: Eti
authors.initials: E
authors.lastname: Broide
authors.affiliation: Microbiology @ Immunology laboratories, Shaare Zedek Medical Center, Jerusalem, Israel.
authors.forename: Roni
authors.initials: R
authors.lastname: Falk
authors.affiliation: Microbiology @ Immunology laboratories, Shaare Zedek Medical Center, Jerusalem, Israel.
authors.forename: Marc
authors.initials: M
authors.lastname: Assous
authors.affiliation: Research Laboratory of Infectious Diseases, Shaare Zedek Medical Center, affiliated to the Hebrew University Medical School, Jerusalem, Israel.|Department of Pediatrics, Shaare Zedek Medical Center, Jerusalem, Israel.
authors.forename: Yechiel
authors.initials: Y
authors.lastname: Schlesinger
mesh_terms: D000328:Adult; D015415:Biomarkers / Q000097:blood; D018414:CD8-Positive T-Lymphocytes / Q000187:drug effects / Q000276:immunology* / Q000473:pathology / Q000821:virology; D003587:Cytomegalovirus / Q000276:immunology*; D003586:Cytomegalovirus Infections / Q000276:immunology / Q000473:pathology / Q000635:transmission* / Q000821:virology; D005260:Female; D005333:Fetus; D006801:Humans; D018445:Infectious Disease Transmission, Vertical; D007371:Interferon-gamma / Q000378:metabolism*; D016013:Likelihood Functions; D010835:Phytohemagglutinins / Q000494:pharmacology; D011247:Pregnancy; D061251:Primary Cell Culture; D011379:Prognosis; D012372:ROC Curve; D014599:Uterus / Q000276:immunology* / Q000473:pathology / Q000821:virology; D014764:Viral Proteins / Q000494:pharmacology
chemical_list: D015415:Biomarkers; D010835:Phytohemagglutinins; D014764:Viral Proteins; D007371:Interferon-gamma