Vascular surgery patients with elevated neutrophil lymphocyte ratios have downregulated neutrophil complement RNA expression.

Elevated NLR (neutrophil-lymphocyte ratio) in elective vascular surgery (EVS) patients is associated with increased mortality independent of perioperative surgical outcome. To understand why high NLR is associated with higher mortality, we investigated neutrophil and lymphocyte transcriptome expression in patients undergoing EVS. Blood samples were collected from patients undergoing EVS and healthy donors for NLR calculation. RNAs were isolated and from subjects' isolated neutrophils and lymphocytes. Patients were divided into NLR_Low (<3) and NLR_High (≥3) groups (n=6 each). Paired Samples with the highest RNA Integrity Number (mean = 9.8+0.4) were sequenced and analyzed for differential expression. Normalized data were inputted for downstream analysis using iPathwayGuide (AdvaitaBio) and gene set enrichment analysis using GenePattern and MSigDB (Broad Institute). There was no clinical difference between the patient groups with regards to clinical diagnosis, age, sex, history of hypertension, lipid abnormalities, diabetes mellitus, smoking or statin use. The mean NLR was 4.37+0.27 (SEM) in NLR_High and 1.88+0.0.16 for NLR_Low group. Significantly differentially expressed gene sets identified in the RNA sequence data were enriched highly (p=1E-24) in humoral immunity and the complement system. Neutrophils from NLR_High patients had downregulation of complement genes (C1QA, C1QB, C1QC, C1S, C2, CR2, C3AR1, C3, C8G, C9, and complement regulatory genes CD59, SERPING1, C4BPA, CFH, and CFI). Downregulation of gene expressions of humoral immunity and complement within the neutrophils are associated with elevated NLR. It remains to be determined if and how these changes contribute to increased late mortality previously observed in patients undergoing EVS.