1729. Profiling Human Neutrophil Functional Responses From Solid-Organ and Stem Cell Transplant Recipients to Candida albicans

Abstract

BackgroundSolid-organ (SOT) and stem cell transplant (SCT) recipients are at increased risk of invasive fungal disease despite normal neutrophil counts in peripheral blood. However, the neutrophils function against fungi has not been completely defined. In this study, we measure human neutrophil anti-candida activity in SOT and SCT recipients.MethodsSOT and SCT patients were identified and consented from September 2018 until April 2019. Healthy control patients (HC) were identified at primary care clinics. EDTA-anticoagulated peripheral blood was obtained from healthy and transplant patients 2–4 months post-transplant. Neutrophils were isolated by negative selection. C. albicans was incubated for 2 hours with and without human neutrophils at multiplicity of infection (MOI) of 10, 5 and 1. Following neutrophil cell lysis, percent remaining live Candida was measured using a viability dye. In addition, growth inhibition of C. albicans by neutrophil swarming to C. albicans spotted onto glass slide arrays was also assessed by live cell imaging.Results22 SOT (15 kidneys, 7 livers), 20 SCT (allograft) and 22 HC were enrolled. Neutrophils from SCT and SOT had lower C. albicans killing percentages compared with HC at MOI 10 (HC: 47%, SOT: 29%, SCT 24% P = 0.0041); MOI 5 (HC: 72%, SOT: 35%, SCT 38% P < 0.0001) and MOI 1 (HC: 91%, SOT: 48%, SCT: 45% P < 0.0001). Neutrophil swarming and fungal control of C. albicans spots was significantly inhibited by neutrophils from SCT when compared with SOT and controls (P <0.0001). Analysis of medications, including tyrosine kinase inhibitor (TKI) use, did not demonstrate significant differences of a specific drug class when patient groups are compared (SCT vs. SOT).ConclusionOur study indicates that despite normal circulating numbers, neutrophils from SOT and SCT recipients are dysfunctional and show profoundly impaired anti-Candida activity. There were no medications or laboratory values that predicted functional neutrophil outcome. These data strongly support the use of functional neutrophil profiling to risk stratify those individuals at higher risk for invasive fungal infections.Disclosures All authors: No reported disclosures.