Title : Impact of fcar methylation on susceptibility and coronary artery lesions in Kawasaki disease
Abstract:
Immunoglobulin (Ig) A is a first-line antibody of mucosal defense and a significant prognostic factor ofcoronary artery lesions (CAL) in Kawasaki disease (KD). We aimed to determine whether DNA methylation ofthe FCAR genes was associated with KD.
Methods
Pre- and post- intravenous immunoglobulin (IVIG) blood samples were collected from 73 KD subjects in thiscase-control study. The DNA methylation levels in the FCAR promoter region were evaluated usingpyrosequencing. Blood samples from 61 controls were also analyzed. FCAR mRNA levels were then analyzedusing a real-time polymerase chain reaction.
Results:
Two CpG sites in the FCAR gene demonstrated a significant elevation in patients without CAL compared tofebrile controls but were not elevated in patients with CAL after therapy. The methylation levels were lower inKD patients with CAL than in non-febrile controls six months after IVIG treatment. We found that FCAR wasmore highly expressed at the mRNA levels in the pre-IVIG KD group than in the post-IVIG groups. FCAR mRNAlevels during inactive disease were significantly lower in patients without CAL compared to those beforetreatment, but not in those with CAL by paired t-test. DNA methylation levels at the FCAR negatively correlatedwith mRNA in the leukocytes.
Conclusions/Learning Points:
This study is the first to identify FCAR methylation and that its expression levels suggest their involvement inboth the development of KD and CAL. Our results revealed that IVIG regulated both the FCAR mRNA andmethylation effectively in the KD patients without CAL. Other methylation or FCAR-modulating agents wouldbe considered for patients with CAL whose FCAR methylation did not respond well to IVIG.
Audience Take Away
- coronary artery lesions
- FCAR expression
- methylation expression
