The effect of FcγRIIA and FcγRIIB on coronary artery lesion formation and intravenous immunoglobulin treatment responses in children with Kawasaki disease

Previous research has found patients with the Fc gamma RIIIB NA1 variant having increased risk of intravenous immunoglobulin (IVIG) resistance in Kawasaki disease (KD). Our previous studies revealed that elevated Fc gamma RIIA expression correlated with the susceptibility of KD patients. We conducted this research to determine whether and how Fc gamma receptors affect the susceptibility, IVIG treatment response, and coronary artery lesions (CAL) of KD patients. The activating Fc gamma RIIA and inhibitory Fc gamma RIIB 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 Fc.RIIA and Fc.RIIB expression levels, as well as a luciferase assay of Fc gamma RIIA. We found a considerable increase in methylation of both Fc gamma RIIA and Fc gamma RIIB in KD patients undergoing IVIG treatment. Promoter methylation of Fc gamma RIIA inhibited reporter activity in K562 cells using luciferase assay. The Fc gamma RIIB mRNA expression levels were not found to increase susceptibility, CAL formation, or IVIG resistance. Fc gamma RIIA mRNA expression levels were significantly higher in IVIG-resistant patients than in those that responded to IVIG during the pre-treatment period. Furthermore, the Fc gamma RIIA/ IIB mRNA expression ratio was considerably higher in KD patients with CAL than in those without CAL. Fc gamma RIIA and Fc gamma RIIB both demonstrated increased methylation levels in KD patients that underwent IVIG treatment. Fc gamma RIIA expression influenced the IVIG treatment response of KD patients. The Fc gamma RIIA/ IIB mRNA expression ratio was greater in KD patients with CAL formation.