Abstract
Previous research has found patients with the FcγRIIIB NA1 variant having increased risk of intravenous immunoglobulin (IVIG) resistance in Kawasaki disease (KD). Our previous studies revealed that elevated FcγRIIA expression correlated with the susceptibility of KD patients. We conducted this research to determine whether and how Fcγ receptors affect the susceptibility, IVIG treatment response, and coronary artery lesions (CAL) of KD patients. The activating FcγRIIA and inhibitory FcγRIIB methylation levels of seven patients with KD and four control subjects were examined using HumanMethylation27 BeadChip. We enrolled a total of 44 KD patients and 10 control subjects with fevers. We performed real-time RT-PCR to determine the FcγRIIA and FcγRIIB expression levels, as well as a luciferase assay of FcγRIIA. We found a considerable increase in methylation of both FcγRIIA and FcγRIIB in KD patients undergoing IVIG treatment. Promoter methylation of FcγRIIA inhibited reporter activity in K562 cells using luciferase assay. The FcγRIIB mRNA expression levels were not found to increase susceptibility, CAL formation, or IVIG resistance. FcγRIIA mRNA expression levels were significantly higher in IVIG-resistant patients than in those that responded to IVIG during the pre-treatment period. Furthermore, the FcγRIIA/IIB mRNA expression ratio was considerably higher in KD patients with CAL than in those without CAL. FcγRIIA and FcγRIIB both demonstrated increased methylation levels in KD patients that underwent IVIG treatment. FcγRIIA expression influenced the IVIG treatment response of KD patients. The FcγRIIA/IIB mRNA expression ratio was greater in KD patients with CAL formation.
Highlights
A type of vasculitis, Kawasaki disease (KD) occurs most commonly in children, surpassing acute rheumatic fever as their leading cause of acquired heart disease [1]
We have demonstrated that Th2 immune-related responses correlated with the susceptibility to KD and disease outcomes, as well as that interleukin-31, which is known to be related to Th2 cytokines, correlated with coronary artery lesions (CAL) when compared to the febrile control subjects [9, 10]
An increase in FcγRIIA mRNA levels was discovered in KD patients [17], but we found no significant differences between the KD patients and the febrile controls with regard to the mRNA levels of FcγRIIB in this study
Summary
A type of vasculitis, Kawasaki disease (KD) occurs most commonly in children, surpassing acute rheumatic fever as their leading cause of acquired heart disease [1]. KD is an acute multi-system vasculitis syndrome that consists of a prolonged fever and at least four of the following five diagnostic criteria: polymorphous rash, www.impactjournals.com/oncotarget Controls. Kawasaki disease mRNA study (N = 10) (N = 44) Age (year) 1.95 ± 0.84 1.52 ± 0.17 Male 6 (60%) 21 (47.8%) Clinical data
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