Baseline serum interleukin-6 to interleukin-2 ratio is associated with the response to seasonal trivalent influenza vaccine in solid organ transplant recipients. Issue 51 (16th December 2015)

• Record Type: Journal Article
• Authors: Fernández-Ruiz, Mario; Humar, Atul; Baluch, Aliyah; Keshwani, Shanil; Husain, Shahid; Kumar, Deepali
• Is Part Of: Vaccine. Volume 33:Issue 51(2015)
• Page Start: 7176
• Page End: 7182
• Publication Date: 2015-12-16
• Subjects: AE adverse event -- CI confidence interval -- CV coefficient of variation -- GC germinal center -- HA hemagglutinin -- HAI hemagglutination inhibition -- IQR interquartile range -- ID intradermal -- IFN interferon -- IL interleukin -- IL-6R interleukin-6 receptor -- IM intramuscular -- LLOQ lowest limit of quantification -- MMF mycophenolate mofetil -- OR odds ratio -- SCF seroconversion factor -- SEM standard error of the mean -- SD standard deviation -- SOT solid organ transplantation -- TFH cell T follicular helper cell -- TIV trivalent inactivated vaccine -- TNF tumor necrosis factor; Influenza vaccination -- Solid organ transplantation -- Vaccine response -- Cytokines -- Interleukin-6 -- Interleukin-2; Vaccines -- Periodicals; 615.372
• DOI: 10.1016/j.vaccine.2015.10.134
• Languages: English
• ISSNs: 0264-410X

Abstract

Highlights: The immunogenicity of seasonal influenza vaccine after solid organ transplantation (SOT) is suboptimal. The analysis of baseline serum cytokines and their kinetics following vaccination may be useful to assess the mechanisms contributing to generate a protective antibody response. Baseline serum IL-6 levels were higher in SOT recipients who achieved vaccine response. Baseline serum IL-2 levels exhibited the opposite association. Baseline IL-6/IL-2 ratio may act as a summary of the cytokine environment modulating the function of CD4 + T follicular helper cells. This ratio was an independent predictor of seroconversion to influenza vaccine antigens after SOT. 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 0.65 pg/mL; P -value = 0.021) and IL-2 levels were lower (0.01 versus 0.50 pg/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 1.72 pg/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.