Back to Search Start Over

FCGR2/3 polymorphisms are associated with susceptibility to Kawasaki disease but do not predict intravenous immunoglobulin resistance and coronary artery aneurysms

Authors :
Paula Uittenbogaard
Stejara A. Netea
Michael W. T. Tanck
Judy Geissler
Piotr Buda
Monika Kowalczyk-Domagała
Magdalena Okarska-Napierała
Diana van Stijn
Carline E. Tacke
US Kawasaki Disease Genetics Consortium
David P. Burgner
Chisato Shimizu
Jane C. Burns
Irene M. Kuipers
Taco W. Kuijpers
Sietse Q. Nagelkerke
Source :
Frontiers in Immunology, Vol 15 (2024)
Publication Year :
2024
Publisher :
Frontiers Media S.A., 2024.

Abstract

IntroductionKawasaki disease (KD) is a pediatric vasculitis that can result in coronary artery aneurysm (CAA) formation, which is a dangerous complication. Treatment with intravenous immunoglobulin (IVIg) significantly decreases the risk of CAA, possibly through competitive binding to Fc-gamma receptors (FcγRs), which reduces the binding of pathological immune complexes. However, ~20% of children have recrudescence of fever and have an increased risk of CAA. Therefore, we aimed to identify genetic markers at the FCGR2/3 locus associated with susceptibility to KD, IVIg resistance, or CAA.Materials and methodsWe investigated the association of single-nucleotide polymorphisms (SNPs) and copy number variations (CNVs) at the FCGR2/3 locus with KD susceptibility, IVIg resistance, and CAA risk using a family-based test (KD susceptibility) and case–control analyses (IVIg resistance and CAA risk) in different cohorts, adding up to a total of 1,167 KD cases. We performed a meta-analysis on IVIg resistance and CAA risk including all cohorts supplemented by previous studies identified through a systematic search.ResultsFCGR2A-p.166His was confirmed to be strongly associated with KD susceptibility (Z = 3.17, p = 0.0015). In case–control analyses, all of the investigated genetic variations at the FCGR2/3 locus were generally not associated with IVIg resistance or with CAA risk, apart from a possible association in a Polish cohort for the FCGR3B-NA2 haplotype (OR = 2.15, 95% CI = 1.15–4.01, p = 0.02). Meta-analyses of all available cohorts revealed no significant associations of the FCGR2/3 locus with IVIg resistance or CAA risk.DiscussionFCGR2/3 polymorphisms are associated with susceptibility to KD but not with IVIg resistance and CAA formation. Currently known genetic variations at the FCGR2/3 locus are not useful in prediction models for IVIg resistance or CAA risk.

Details

Language :
English
ISSN :
16643224
Volume :
15
Database :
Directory of Open Access Journals
Journal :
Frontiers in Immunology
Publication Type :
Academic Journal
Accession number :
edsdoj.9d532690a7a4cb8a2bb92fcfcd67cc3
Document Type :
article
Full Text :
https://doi.org/10.3389/fimmu.2024.1323171