Proteomic Profiles of Neutrophils from Behcet's Uveitis Patients and their Sex Differences

Abstract

Behcet's uveitis (BU) is one of the most vision-threatening uveitis entities with male-biased incidence and severity. Neutrophil dysfunction has been implicated in the pathogenesis of this disease. However, their proteomic changes are not completely understood. We performed proteomic analysis on peripheral neutrophils from patients with active BU and identified 82 up-regulated and 516 down-regulated differentially expressed proteins (DEPs) compared to healthy controls (HCs). We further performed functional analysis on these DEPs and found that the pathway involved in neutrophil extracellular trap formation was activated, whereas nucleotide metabolism and apoptosis were suppressed. Compared with female patients, male patients presented enhanced pathways associated neutrophil-mediated inflammatory responses and suppressed apoptosis. Additionally, integrative analysis of proteomic profiles and single-cell RNA sequencing (scRNA-seq) data revealed that these sex differences might be related to the enhanced inflammatory response in primed inflammatory and inflammatory neutrophils as well as deficiencies in apoptosis and nucleotide metabolism in ROS-responsive neutrophils. Collectively, our data revealed the proteomic profiles of neutrophils from patients with BU, and their functional changes may play crucial roles in the pathogenesis of this disease and its sex differences.

Keywords: Apoptosis; Behcet's uveitis; Neutrophil hyperactivation; Nucleotide metabolism; Proteomics.