Major methylation alterations on the CpG markers of inflammatory immune associated genes after IVIG treatment in Kawasaki disease.

BACKGROUND: Kawasaki disease (KD) is an autoimmune disease preferentially attacking children younger than five years worldwide. So far, the principal treatment to KD is the administration of Intravenous immunoglobulin (IVIG). Although DNA methylation plays important regulation roles in diseases, few studies investigated the regulation roles of DNA methylation in KD.

METHODS: In this study, we focused not only on the DNA methylation alterations resulted from KD onset but also on DNA methylation alterations resulted from IVIG administration. To do so, we investigated the effects of KD's onset and IVIG administration on CpG marker's methylation alterations.

RESULTS: We first found that DNA methylation alterations reflecting disease onset or IVIG administration are contributed mainly by the CpG markers on autosomes. In addition, we also demonstrated that some CpG markers carry methylation alteration among samples, forcing the expression abundance of the downstream genes to be also altered and negatively correlated with methylation profile. Finally, compared with KD's onset, IVIG administration brings stronger impact on methylation alteration. And, such alterations were conducted mainly by hyper-methylating CpG markers, forcing the corresponding genes to keep lower expression levels. Moreover, the genes regulated by the altered CpG markers with IVIG administration are enriched in the pathways associated with inflammatory immune response.

CONCLUSIONS: In summary, our result provides researchers with another way into the regulation mechanism through which IVIG represses excessive inflammatory responses.