TARC/CCL17 gene polymorphisms and expression associated with susceptibility and coronary artery aneurysm formation in Kawasaki disease

Abstract

Background: Kawasaki disease (KD) is a systemic vasculitis of unknown etiology. Thymus and activation-regulated chemokine/chemokine ligand 17 (TARC/CCL17) is one of the Th2 chemokines and has been suggested as a candidate gene for conferring susceptibility to Th2 associated with allergy diseases. This study examined the correlation between gene polymorphisms and plasma levels of TARC/CCL17 in patients with KD and the outcomes of KD. Methods: A total of 381 KD patients and 564 controls were subjected to determination of five tagging single-nucleotide polymorphisms of TARC/CCL17. In addition, plasma TARC/ CCL17 levels were measured by enzyme-linked immunosorbent assay. results: Polymorphisms of TARC/CCL17 were significantly different between normal children and patients with KD. A allele of rs4784805 has better intravenous immunoglobulin (IVIG) treatment response to KD. Furthermore, plasma TARC/ CCL17 levels were higher in KD patients than that in controls before IVIG treatment. After IVIG treatment, plasma TARC/ CCL17 levels decreased significantly. conclusion: This study provides the first evidence supporting the association between TARC/CCL17 polymorphisms, susceptibility of KD, and IVIG responses in KD patients. k awasaki disease (KD), also known as mucocutaneous lymph node syndrome, is an acute febrile systemic vasculitis that was first described by Kawasaki et al. in 1974 in English (1), but its etiology remains unknown till now. It occurs most commonly in children younger than 5 y of age, particularly in children younger than 2 y of age, and the clinical presentation of KD is prolonged fever, conjunctivitis, diffuse mucosal inflammation, polymorphous skin rashes, indurative edema of the hands and feet associated with peeling of finger tips, and nonsuppurative lymphadenopathy (2). In developed countries, KD has been the leading cause of acquired heart diseases in children (2,3). The most serious complication of KD is the occurrence of coronary artery lesions (CALs), including myocardial infarction, coronary artery fistula formation (4), coronary artery dilation, or coronary artery aneurysm (CAA) (5). In addition, KD is the major cause of acquired CAA in childhood (6). The prevalence of KD in children is the highest in Japan, followed by Korea and Taiwan, and the lowest in Europe (5). Therefore, it is possible that a genetic background plays an important role in the pathogenesis of KD.Thymus and activation-regulated chemokine/chemokine ligand 17 (TARC/CCL17) is a member of the CC chemokine group (7). It is a ligand of the CC chemokine receptor (8), which is selectively expressed on Th2 cells (9) and serves for the recruitment and migration of cells bearing this receptor (7-9). TARC/CCL17 has been suggested as a candidate gene for conferring susceptibility to Th2 associated with allergy diseases and is highly implicated in the pathogenesis of atopic dermatitis (10,11) and bronchial asthma (12). There are several lines of evidence pointing out an abnormal Th1/Th2 balance in KD patients (13). Recently, it has b...

IL-31 Associated with Coronary Artery Lesion Formation in Kawasaki Disease

“…Th2 immune response included IL-4 [7], IL-5, eosinophil [8] and CCL17 [9] were also reported to play some role in the immuneopathogenesis and outcome of KD [10]. Eosinophilia associated with KD was first described by Dr. Kawasaki et al [1] and was also found in coronary artery autopsies [11].…”

Association Between a <i>CCL17</i> Genetic Variant and Risk of Coronary Artery Disease in a Chinese Han Population

“…14, 15 Recently, Lee et al found that CCL17 gene polymorphisms and their expression were associated with susceptibility and the formation of coronary artery aneurysms in Kawasaki disease. 16 Several previous studies have reported that the CCL17 SNP rs223828 (previously known as −431C>T) is associated with increased CCL17 expression. For example Sekiya et al found that subjects carrying the −431T allele had significantly higher serum CCL17 concentrations than those without this allele, indicating that the −431T allele may have a major effect on CCL17 production.…”

Association of the polymorphisms in Th2 chemotaxis-related genes with the development and prognosis of autoimmune thyroid diseases

“…Low frequency of T allele may promote Th1 reaction which was associated with the pathogenesis of multiple sclerosis [43]. On the other hand, although T allele was less frequent in patients with Kawasaki disease, TARC level was higher in them than in control subjects [42], but this may be because duration of fever in these patients were longer than in controls [42]. Therefore, we suggest that this SNP may be associated with chemotaxis of Th2 cells.…”

“…TARC/ CCL17 induces the recruitment and migration of Th2 cells, affecting the susceptibility of Th2-associated disease such as atopic dermatitis and bronchial asthma [39,40]. The frequency of the T allele of the rs223828 SNP, which has higher transcription activity, was lower in patients of Kawasaki disease and multiple sclerosis than in controls [41][42][43]. Low frequency of T allele may promote Th1 reaction which was associated with the pathogenesis of multiple sclerosis [43].…”