title: The effect of FcγRIIA and FcγRIIB on coronary artery lesion formation and intravenous immunoglobulin treatment responses in children with Kawasaki disease.
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.
authors.affiliation: Kawasaki Disease Center, Kaohsiung Chang Gung Memorial Hospital, Kaohsiung, Taiwan.|Graduate Institute of Clinical Medical Sciences, College of Medicine, Chang Gung University, Kaohsiung, Taiwan.|Department of Pediatrics, Kaohsiung Chang Gung Memorial Hospital and Chang Gung University College of Medicine, Kaohsiung, Taiwan.
authors.forename: Ling-Sai
authors.initials: LS
authors.lastname: Chang
authors.affiliation: Kawasaki Disease Center, Kaohsiung Chang Gung Memorial Hospital, Kaohsiung, Taiwan.|Department of Pediatrics, Kaohsiung Chang Gung Memorial Hospital and Chang Gung University College of Medicine, Kaohsiung, Taiwan.
authors.forename: Mao-Hung
authors.initials: MH
authors.lastname: Lo
authors.affiliation: Genomics and Proteomics Core Laboratory, Department of Medical Research, Kaohsiung Chang Gung Memorial Hospital and Chang Gung University College of Medicine, Kaohsiung, Taiwan.
authors.forename: Sung-Chou
authors.initials: SC
authors.lastname: Li
authors.affiliation: Graduate Institute of Clinical Medical Sciences, College of Medicine, Chang Gung University, Kaohsiung, Taiwan.|Department of Otolaryngology, Kaohsiung Chang Gung Memorial Hospital and Chang Gung University College of Medicine, Kaohsiung, Taiwan.
authors.forename: Ming-Yu
authors.initials: MY
authors.lastname: Yang
authors.affiliation: Kawasaki Disease Center, Kaohsiung Chang Gung Memorial Hospital, Kaohsiung, Taiwan.|Department of Pediatrics, Kaohsiung Chang Gung Memorial Hospital and Chang Gung University College of Medicine, Kaohsiung, Taiwan.
authors.forename: Kai-Sheng
authors.initials: KS
authors.lastname: Hsieh
authors.affiliation: Kawasaki Disease Center, Kaohsiung Chang Gung Memorial Hospital, Kaohsiung, Taiwan.|Department of Pediatrics, Kaohsiung Chang Gung Memorial Hospital and Chang Gung University College of Medicine, Kaohsiung, Taiwan.
authors.forename: Ho-Chang
authors.initials: HC
authors.lastname: Kuo
mesh_terms: D061605:Administration, Intravenous; D054316:Biomarkers, Pharmacological / Q000032:analysis; D016022:Case-Control Studies; D002675:Child, Preschool; D003324:Coronary Artery Disease / Q000150:complications / Q000188:drug therapy* / Q000235:genetics*; D016903:Drug Monitoring / Q000379:methods; D005260:Female; D020022:Genetic Predisposition to Disease; D006801:Humans; D016756:Immunoglobulins, Intravenous / Q000008:administration & dosage*; D007223:Infant; D008297:Male; D009080:Mucocutaneous Lymph Node Syndrome / Q000150:complications / Q000188:drug therapy* / Q000235:genetics; D017452:Receptors, IgG / Q000235:genetics*
chemical_list: D054316:Biomarkers, Pharmacological; C445323:FCGR2A protein, human; C499173:FCGR2B protein, human; C080568:Fc gamma receptor IIA; D016756:Immunoglobulins, Intravenous; D017452:Receptors, IgG
keywords: FcγRIIA; FcγRIIB; Immune response; Immunity; Immunology and Microbiology Section; Kawasaki disease; coronary artery lesions; intravenous immunoglobulin