HLA–E gene polymorphism associated with susceptibility to kawasaki disease and formation of coronary artery aneurysms

Abstract

Objective. Kawasaki disease (KD) is a pediatric systemic vasculitis of unknown cause for which a genetic influence is supposed. The purpose of this study was to identify possible genetic variants in the major histocompatibility complex (MHC) region that are associated with KD and the development of coronary artery aneurysms (CAAs) in a Taiwanese population.Methods. The 168 genetic variants covering the MHC locus were analyzed in an association study of a Taiwanese cohort of 93 KD patients and 680 unrelated healthy children matched for sex and age with the study patients.Results. Eleven single-nucleotide polymorphisms (SNPs) were associated with the occurrence of KD. The SNP located at the 3 -untranslated region of HLA-E (rs2844724) was highly associated (P < 1 ؋ 10 ؊7 ). In addition, the frequency of the C allele was higher in KD patients without CAAs than in controls (P < 0.001) due to a significantly increased frequency of the CC and CT genotypes. Plasma levels of soluble HLA-E were significantly higher in KD patients than in controls regardless of the presence of CAAs. Furthermore, there was a trend toward higher plasma levels of soluble HLA-E in KD patients with the CT and TT genotypes of the HLA-E gene polymorphism.Conclusion. Our results suggest that the HLA-E gene polymorphism may play a role in the pathogenesis of KD.

Responsiveness to intravenous immunoglobulins and occurrence of coronary artery abnormalities in a single-center cohort of Italian patients with Kawasaki syndrome

“…This observation has been confirmed by studies of surveillance in larger groups of patients with KS from Japan, Korea and Taiwan [17][18][19]. Possible genetic variants in the major histocompatibility complex region that are associated with KS might influence the responsiveness to IVIG and the development of CAA [20,21].…”

Therapeutic preparations of IVIg contain naturally occurring anti–HLA-E antibodies that react with HLA-Ia (HLA-A/-B/-Cw) alleles

“…However, administration of IVIg reduces coronary artery abnormalities such as aneurisms from 20% to 25% to 3% to 5% within 10 days of illness onset. 43 Recently, Lin et al 44 highlighted the role of HLA-E in the pathogenesis of KD. They measured plasma concentrations of soluble HLA-E (sHLA-E) by enzyme-linked immunosorbent assay in 96 Taiwanese patients with KD and in 93 healthy controls.…”

Genetic polymorphisms in Kawasaki disease

“…However, other studies have revealed inconsistent results (Table 1) [45][46][47][48][49][50][51][52][53][54][55][56][57] . These results indicate that the genes responsible for susceptibility and CAL formation may be different between populations [7,32,37,38,[58][59][60] . Recently, several candidate genes have been proposed for (Table 2).…”

“…For example, a number of genes have been reported to have significant associations with the susceptibility to KD in different populations. For instance, single nucleotide polymorphisms (SNPs) in the monocyte chemoattractant protein 1 (MCP-1) [29] , IL-10 [30][31][32] , CD40L [33] , IL-4 [26] , CASP3 [20,34] , IL-18 [35] , IL-1B [36] , HLA-E [37] , C-C chemokine receptor 5 (CCR5) [38] , and inositol 1, 4, 5-trisphosphate 3-kinase C (ITPKC) [21,39] have been reported to be associated with the development of KD. In early 2011, Shimizu et al [12] first reported that genetic polymorphisms of TGFB2, TGFBR2, and SMAD3 are associated with susceptibility to Kawasaki disease and the development of coronary artery lesions.…”