Systems analysis of influenza vaccine response in chronic dialysis patients reveals altered immunometabolism 9399

Description Chronic kidney disease is a life-threatening condition that can lead to dependence on chronic dialysis (CD) therapy. Though CD patients have immune impairments, influenza vaccine responses in the pediatric CD population are unknown. We hypothesized that CD patients exhibit impaired innate and adaptive immune responses to influenza vaccination compared to healthy children (HC). To test this hypothesis, we vaccinated 14 HC and 7 CD patients with the influenza vaccine and collected blood samples pre- and post-vaccination. We performed RNA sequencing and hemagglutination inhibition assays to evaluate the transcriptional and antibody responses, respectively. Post-vaccination, both HC and CD patients exhibited an increase in innate immune signatures at day 3 post-vaccination, including in TLR signaling and interferon response pathways. At day 7, HC and CD both showed increases in adaptive immune signatures, particularly in B and plasma cell modules. However, CD patients exhibited perturbation in certain metabolic pathways, including electron transport and inositol phosphate, throughout the time course. Despite these distinct transcriptional signatures, there was no difference in antibody responses to vaccination between HC and CD patients, although high pre-vaccination titers may have limited the analysis. Together, this study highlights differences in vaccine responses in CD patients compared to HC that may affect protection against influenza.