Bioinformatics identification of hub genes and signaling pathways regulated by intravenous immunoglobulin treatment in acute Kawasaki disease

Abstract

Kawasaki disease (KD) is an acute, self-limiting form of vasculitis commonly encountered in infants and young children. Intravenous immunoglobulin (IVIG) is the primary drug used for the treatment of KD, which may significantly reduce the occurrence of coronary artery lesions. However, the specific molecular profile changes of KD caused by IVIG treatment have remained elusive and require further research. The present study was designed to identify key genes, pathways and immune cells affected by IVIG treatment using multiple bioinformatics analysis methods. The results suggested that myeloid cells and neutrophils were affected by IVIG treatment. Kyoto Encyclopedia of Genes and Genomes pathway analysis identified that hematopoietic cell lineages and osteoclast differentiation may have an important role in the mechanism of action of IVIG treatment. Immune cell analysis indicated that the levels of monocytes, M1 macrophages, neutrophils and platelets were markedly changed in patients with KD after vs. prior to IVIG treatment. The key upregulated genes, including ZW10 interacting kinetochore protein, GINS complex subunit 1 and microRNA-30b-3p in whole blood cells of patients with KD following treatment with IVIG indicated that these IVIG-targeted molecules may have important roles in KD. In addition, these genes were further examined by literature review and indicated to be involved in cell proliferation, apoptosis and virus-related immune response in patients with KD. Therefore, the present results may provide novel insight into the mechanisms of action of IVIG treatment for KD.

Nomogram to predict risk of resistance to intravenous immunoglobulin in children hospitalized with Kawasaki disease in Eastern China

“…Intravenous immunoglobulin (IVIG) is the most effective initial treatment for acute symptoms, but 10–20% of patients will have IVIG resistance and remain at risk for developing coronary artery lesions [ 2 ]. The mechanism of action of IVIG in Kawasaki disease is still not understood [ 3 ], and the factors influencing IVIG resistance have not yet been identified. In patients who show IVIG resistance, subsequent treatment is not as effective [ 4 , 5 ].…”

The role of FOXO4/NFAT2 signaling pathway in dysfunction of human coronary endothelial cells and inflammatory infiltration of vasculitis in Kawasaki disease

“…Kawasaki disease (KD) is an acute vasculitis that is self−limiting and affects children. In developed countries, KD represents the most common cause of childhood acquired heart disease ( 1 ). Serious complications include coronary artery disease, which is closely related to the incidence of cardiovascular disease, especially coronary heart disease in adulthood ( 2 ), thus, a deeper mechanistic understanding of KD is required.…”