Long-Term Hypermethylation of FcγR2B in Leukocytes of Patients with Kawasaki Disease

The Fc gamma receptor family contains several activating receptors and the only inhibitory receptor, Fc gamma R2B. In this study, we investigated the dynamic methylation change of Fc gamma R2B in different stages of Kawasaki disease (KD). We enrolled a total of 116 participants, which included patients with febrile diseases as controls and KD patients. Whole blood cells of KD patients were collected prior to intravenous immunoglobulin (WIG) treatment (KD1), three to seven days after WIG (KD2), three weeks after IVIG treatment (KD3), six months after WIG (KD4), and one year after WIG treatment (KD5). In total, 76 KD patients provided samples in every stage. Leukocytes of controls were also recruited. We performed DNA extraction and pyrosequencing. Fc gamma R2B methylation levels were higher in KD3 compared to both the controls and KD1. A significantly higher methylation of Fc gamma R2B was found in KD5 when compared with KD1. Fc gamma R2B methylation levels in the IVIGresistant group were lower than those in the WIG-responsive group at KD1-3 (p = 0.004, 0.004, 0.005 respectively). This study is the first to report the dynamic change of Fc gamma R2B methylation and to demonstrate long-term hypermethylation one year after disease onset. Hypomethylation of Fc gamma R2B is associated with IVIG resistance.

Automated summary

This study examined the dynamic methylation changes of FcγR2B in different stages of Kawasaki disease, revealing a long-term hypermethylation of FcγR2B one year after disease onset and the association of hypomethylation with IVIG resistance.