title: Baseline serum interleukin-6 to interleukin-2 ratio is associated with the response to seasonal trivalent influenza vaccine in solid organ transplant recipients.
abstract: BACKGROUND
  The analysis of pre- and post-vaccination B-cell-associated cytokines might be useful in predicting the immunogenicity of seasonal trivalent influenza vaccine (TIV) in solid organ transplant (SOT) recipients.
  
  
  METHODS
  We performed a subanalysis of a clinical trial that compared the safety and efficacy of high-dose intradermal (ID) versus intramuscular (IM) TIV in SOT recipients. Serum levels of selected cytokines (interferon [IFN]-γ, interleukin [IL]-2, IL-4, IL-5, IL-6, IL-12 and IL-21, and tumor necrosis factor [TNF]-α) were measured pre- and one month post-vaccination in 155 patients (with 84 and 71 receiving the ID and IM vaccines, respectively). Cytokine profiles were compared according to vaccine response (seroconversion [≥4-fold increase in hemagglutination inhibition antibody titers] to ≥1 influenza vaccine antigen).
  
  
  RESULTS
  Mean baseline IL-6 levels were higher (1.20 versus 0.65pg/mL; P-value=0.021) and IL-2 levels were lower (0.01 versus 0.50pg/mL; P-value=0.051) in patients achieving vaccine response. After adjusting for clinical variables, baseline IL-6/IL-2 ratio remained predictive of vaccine response (odds ratio per 10-unit increment: 1.06; 95% confidence interval: 1.02-1.10; P-value=0.002). Vaccination induced an increase in TNF-α (P-value <0.0001) and a decrease in IL-5 levels (P-value=0.0007). There were no significant differences in cytokine kinetics between vaccine responders and non-responders. Mean baseline TNF-α levels were higher in patients experiencing moderate-to-severe adverse events after vaccination (1.93 versus 1.72pg/mL; P-value=0.009).
  
  
  CONCLUSIONS
  Baseline serum IL-6 and IL-2 levels, two cytokines that modulate the role of CD4(+) T follicular helper cells and the terminal differentiation of B-cells, predict vaccine response in SOT recipients.
authors.affiliation: Multi-Organ Transplant Program, University Health Network, Toronto, Ontario, Canada.
authors.forename: Mario
authors.initials: M
authors.lastname: Fernández-Ruiz
authors.affiliation: Multi-Organ Transplant Program, University Health Network, Toronto, Ontario, Canada.
authors.forename: Atul
authors.initials: A
authors.lastname: Humar
authors.affiliation: Division of Infectious Diseases, Moffitt Cancer Center, Tampa, FL, United States.
authors.forename: Aliyah
authors.initials: A
authors.lastname: Baluch
authors.affiliation: Multi-Organ Transplant Program, University Health Network, Toronto, Ontario, Canada.
authors.forename: Shanil
authors.initials: S
authors.lastname: Keshwani
authors.affiliation: Multi-Organ Transplant Program, University Health Network, Toronto, Ontario, Canada.
authors.forename: Shahid
authors.initials: S
authors.lastname: Husain
authors.affiliation: Multi-Organ Transplant Program, University Health Network, Toronto, Ontario, Canada. Electronic address: Deepali.Kumar@uhn.ca.
authors.forename: Deepali
authors.initials: D
authors.lastname: Kumar
mesh_terms: D000328:Adult; D000368:Aged; D003661:Decision Support Techniques; D005260:Female; D006801:Humans; D007252:Influenza Vaccines / Q000008:administration & dosage / Q000276:immunology*; D007251:Influenza, Human / Q000517:prevention & control*; D007271:Injections, Intradermal; D007273:Injections, Intramuscular; D007376:Interleukin-2 / Q000097:blood*; D015850:Interleukin-6 / Q000097:blood*; D008297:Male; D008875:Middle Aged; D011446:Prospective Studies; D044967:Serum / Q000737:chemistry; D066027:Transplant Recipients; D019737:Transplants; D016896:Treatment Outcome
chemical_list: D007252:Influenza Vaccines; D007376:Interleukin-2; D015850:Interleukin-6
keywords: Cytokines; Influenza vaccination; Interleukin-2; Interleukin-6; Solid organ transplantation; Vaccine response