Neutrophil Extracellular Traps Formation and Citrullinated Histones 3 Levels in Patients with Kawasaki Disease.

Abstract

Background: Kawasaki disease (KD) is a vasculitis associated with vascular injury and autoimmune response. Inflammatory factors stimulate neutrophils to produce web-like structures called neutrophil extracellular traps (NETs). Citrullinated histone 3 (H3Cit) is one of the main protein components of neutrophil extracellular traps involved in the process of NETosis. The levels of NETs and H3Cit in the KD are not known.

Objective: To determine the changes in the levels of NETs and H3Cit in KD.

Methods: Children with KD were recruited and divided into the acute KD and the sub-acute KD group according to the disease phase and whether intravenous immunoglobulin (IVIG) was used or not. Peripheral venous blood was taken before and after the IVIG administration and sent for the examination of NETs by flow cytometry. The level of H3Cit was measured by enzyme-linked immunosorbent assay (ELISA).

Results: The counts of NETs in the acute KD group significantly increased compared with the healthy controls (p<0.01). The level of H3Cit was significantly higher in the acute KD group than in the healthy control subjects. Of note, both the counts of NETs and the level of H3Cit decreased in the KD patients treated with IVIG compared with the acute KD group (p<0.01).

Conclusion: Acute KD is characterized by an increased formation of NETs and high levels of H3Cit. IVIG significantly inhibited NETs formation and also reduced the level of plasma H3Cit in children with KD.