Low-dose methotrexate therapy for intravenous immunoglobulin-resistant Kawasaki disease

Purpose

The aim of this study was to evaluate the efficacy of low-dose oral methotrexate (MTX) as a treatment for patients with Kawasaki disease (KD) which was resistant to intravenous immunoglobulin (IVIG).

Patients and Methods

The patients who had persistent or recrudescent fever after treatment with IVIG were subsequently treated with low-dose oral MTX [10 mg/body surface area (BSA)] once weekly.

Results

Seventeen patients developed persistent or recrudescent fever after treatment of KD with IVIG and were consequently given MTX. The proportion of children with coronary artery lesions (CALs) was 76%. The median value of maximum body temperatures decreased significantly within 24 hours of MTX therapy (38.6℃ vs. 37.0℃, p < 0.001). The median CRP (C-reactive protein) level was found to be significantly lower 1 week after administering the first dose of MTX (8.9 mg/dL vs. 1.2 mg/dL, p < 0.001). The median duration of fever before MTX treatment was shorter in CALs (-) group than in CALs (+) group (7 days vs. 10 days, p = 0.023). No adverse effects of MTX were observed.

Conclusion

MTX treatment for IVIG-resistant KD resulted in quick resolution of fever and rapid improvement of inflammation markers without causing any adverse effects. MTX therapy should further be assessed in a multicenter, placebo-blinded trial to evaluate whether it also improves coronary artery outcome.     

70例不完全川崎病临床分析

目的总结不完全川崎病（incomplete KD）的临床特征,以便早期诊治,减轻冠状动脉的病变程度,改善预后。方法回顾性分析2006年1月—2008年12月期间70例住院不完全KD患儿的临床资料：（1）总结不完全性KD的临床特征;（2）分析不完全KD出现冠状动脉病变（coronary artery lesion,CAL）的高危因素（3）总结静脉注射免疫球蛋白对不完全KD的疗效;（4）随访观察其中的患儿,比较IVIG400mg/kg、1g/kg和2g/kg治疗的远期疗效。结果 （1）70例不完全KD中结膜充血出现最早,其他临床症状发生出现较晚;（2）不完全KD发生冠状动脉病变,以冠状动脉扩张的发生率最高;（3）不完全KD发生冠状动脉病变与年龄、性别、血小板、CRP、ESR和接受IVIG的时间有密切关系（P〈0.05）。（4）IVIG400mg/kg较1g/kg和2g/kg治疗组的CAL发生率明显增高,具有统计学意义（P〉0.05）;1g/kg和2g/kg治疗组的CAL发生率差异不大,无统计学意义。结论 （1）不完全KD的临床表现不典型,指趾端脱皮可以作为不完全性KD的诊断依据之一,而超声心动图对不完全KD的早期诊断更为重要;（2）年龄、性别、血小板、CRP、ESR和接受IVIG的时间是不完全KD发生冠状动脉病变的高危因素,不完全KD发生冠状动脉病变以冠状动脉扩张最为常见;（3）IVIG1g/kg和2g/kg治疗不完全KD的疗效相似,较400mg/kg治疗KD的疗效佳。     

Relationship between IL-27 and coronary arterial lesions in children with Kawasaki disease

Kawasaki disease (KD) arises due to the disorder of the inflammation response and faulty immune regulation. Interleukin-27 (IL-27) is a novel cytokine with both pro-inflammatory and anti-inflammatory effects. This study investigated the relationship between serum levels of IL-27, Interleukin-17A (IL-17A), Interleukin-10 (IL-10), Interleukin-6 (IL-6), Interleukin-1β (IL-1β), tumor necrosis factor-α (TNF-α) and coronary artery lesions (CALs) in patients with KD. We obtained blood samples from 81 children with KD before intravenous immunoglobulin (IVIG) therapy. Levels of IL-27, IL-17A, IL-10, IL-6, IL-1β and TNF-α were measured in 251 cases, including 4 groups: the normal control group, NC (n = 90), febrile control, FC (n = 80), KD without coronary arteries (n = 41) and KD with coronary arterial lesions (n = 40). White blood cells counts (WBC), red blood cells counts (RBC), hemoglobin, C-reactive protein (CRP), erythrocyte sedimentation rate and procalcitonin (PCT) were tested in all subjects. Levels of IL-27, IL-10, IL-17A, IL-6, IL-1β and TNF-α were significantly elevated, and RBC and hemoglobin significantly decreased in the group of KD group compared with febrile and control groups. IL-27, IL-6, IL-1β and TNF-α serum levels are even higher in KD children with CALs. There was positive relationship between serum levels of IL-27 and WBC, CRP, PCT, IL-10, IL-17A, IL-6 and TNF-α in children with KD. The up-regulation of IL-27 may be closely linked to up-regulation of systemic pro-inflammatory markers in acute KD. Morover, IL-27 may be involved in the development of CALs in acute KD.     

Lack of Association of the Vascular Endothelial Growth Factor Gene Polymorphisms with Kawasaki Disease in Taiwanese Children

INTRODUCTION: Kawasaki disease (KD) is an acute febrile vasculitis of unknown etiology that mainly occurs in infants and children. Clinical and histopathologic findings suggest that vascular endothelial growth factor (VEGF) is involved in the coronary artery lesions (CALs) development in KD. This study hypothesized that specific VEGF gene polymorphisms and their haplotypes are associated with KD susceptibility and CAL development in Taiwanese children. SUBJECTS AND METHODS: The VEGF -2578 A/C, -634 G/C, and +936 C/T single-nucleotide polymorphisms (SNPs) were genotyped in 156 children with KD and 672 ethnically matched healthy controls using the Pre-Developed TaqMan Allelic Discrimination Assay. RESULTS: No significant differences in genotype, allele, carrier, and haplotype frequencies of the three SNPs were found between healthy controls and children with KD or between patients with and without CAL. CONCLUSION: Our data suggest that VEGF -2578 A/C, -634 G/C, and +936 C/T SNPs do not confer increased susceptibility to KD or to CAL development.     

Risk factors for failure of initial intravenous immunoglobulin treatment in Kawasaki disease

The aims of this study were to determine the occurrence and variables associated with the initial intravenous immunoglobulin (IVIG) treatment failure in Kawasaki disease (KD) and to categorize differences in clinical characteristics between responders and nonresponders to initial IVIG treatment. Patients were classified into two groups. Group A included 33 patients who received a single dose of IVIG treatment and responded. Group B included 18 patients who received more than two doses of IVIG due to failure of the initial treatment. The mean duration of fever after initial treatment in group B was significantly longer than it was in group A. In group B, we found that higher bilirubin, aspartate aminotransferase (AST), polymorphonuclear cells (PMN) (%), and lower platelet values at baseline were independent predictors of persistent or recurrent fever in patients with KD. Coronary artery abnormalities were found in 8 patients (44.4%) in group B and in two patients (6.1%) in group A. We found that abnormal liver function tests and a lower platelet count at baseline were possible predictors of nonresponders to IVIG in patients with KD. There is a need for a prospective study focused on baseline hepatobiliary parameters.     

Association of COL11A2 polymorphism with susceptibility to Kawasaki disease and development of coronary artery lesions

Kawasaki disease (KD) is a pediatric systemic vasculitis of unknown etiology wherein genetic influence is suspected. Gene clusters within the HLA region at chromosome 6p21.3 have been linked to KD and other autoimmune disorders. As collagen is a strong autoantigen inducing chronic inflammation in patients with vasculitis, this study tests a hypothesis that single-nucleotide polymorphism (SNP) of a collagen gene, COL11A2, located in this HLA region may affect susceptibility to Kawasaki disease and its arterial sequels. SNP sites rs2294478 (at promoter) and rs2076311 (at intron 19) were genome-typed on 93 KD patients and 680 healthy subjects. Genotypic and allelic frequencies analyses found A allele at rs2076311 as a risk allele for KD. Clinical association study showed protective potential of C/C genotype at rs2294478 and A/A at rs2076311 for developing coronary artery lesions (CALs) in patients. In addition, C-A haplotype of COL11A2 gene associates with KD development and can serve as a genetic marker to differentiate KD patients lacking CALs from those with such lesions. Our findings suggest the involvement of genetic variations of COL11A2 in Kawasaki disease and CAL formation.     

CD40L、可溶性黏附分子及MMP9在川崎病中的表达及意义

目的：研究T细胞CD40配体（CD40L）、血浆中可溶性E选择素（sE-selectin）、可溶性细胞间黏附分子1（sICAM-1）和基质金属蛋白酶9（MMP9）在川崎病中的表达及意义。方法：用流式细胞双色荧光标记技术检测20例川崎病急性期及静脉注射免疫球蛋白（IVIG）治疗后的患儿，19例正常对照，外周血T细胞表达CD40L阳性细胞率及平均荧光强度；用ELISA方法检测上述3组血浆中sE—selectin、sICAM-1和MMP9水平。结果：急性期川崎病组T细胞CD40L表达明显高于IVIG治疗后组（P〈0．05），川崎病患儿T细胞CD40L表达较正常对照持久；2例伴冠状动脉损害（CAL）的川崎病患儿急性期T细胞CD40L表达高于无CAL者。急性期川崎病组血浆sICAM-1、MMP9明显高于IVIG治疗后组，急性期川崎病患儿血浆sE—selectin、sICAM—1明显高于正常对照（P〈0.05）。川崎病急性期T细胞表达CD40L与血浆sE—selectin、sICAM-1、MMP9水平无明确相关性（P〉0．05）。结论：T细胞表达CD40L升高在川崎病血管炎及冠状动脉病变中可能起一定作用。血浆sE-selectin、sLCAM-1和MMP9水平可作为反映川崎病血管炎的指标。     

The -590 C/T and 8375 A/G interleukin-4 polymorphisms are not associated with Kawasaki disease in Taiwanese children

Although some previous studies have reported that genetic and immunologic factors play important roles in the pathogenesis of Kawasaki disease (KD), the etiologic factors of this enigmatical pediatric disease are still poorly understood. This study aims to investigate whether polymorphisms of the interleukin-4 gene (IL-4; -590 C/T in the promoter region and 8375 A/G in intron 3) are associated with KD and the development of coronary artery lesions (CALs) in Taiwanese children. Genomic DNA was extracted from whole-blood samples from 150 children with KD and 472 ethnically matched healthy control subjects. The IL-4 -590 C/T and 8375 A/G single nucleotide polymorphisms (SNPs) were genotyped by a real-time polymerase chain reaction system with the Pre-Developed TaqMan Allelic Discrimination Assay. No significant associations between IL-4 SNPs and susceptibility of KD with CALs were found. In addition, no evidence for associations between IL-4 SNPs and CAL development was found. These results suggest that IL-4 -590 C/T and 8375 A/G SNPs do not confer a relevant role in the susceptibility or CAL development of KD in Taiwanese children.     

Immune‐monitoring in Kawasaki disease patients treated with infliximab and intravenous immunoglobulin

The expansion of regulatory T cells (T_reg) controls inflammation in children with acute Kawasaki disease (KD). Blockade of tumour necrosis factor (TNF)-α is an emerging therapy for KD patients with refractory inflammation, but there is concern that this therapy could impede the host immune regulation. To define the effect of TNF-α blockade, we conducted ex-vivo immune-monitoring in KD subjects who participated in a randomized, double-blind, placebo-controlled clinical trial of the addition of infliximab to standard intravenous immunoglobulin (IVIG) therapy. We enumerated circulating myeloid and plasmocytoid dendritic cells (DC), regulatory T cells (T_reg) and memory T cells (T_mem) in 14 consecutive, unselected KD patients (seven treated with IVIG, seven with IVIG + infliximab) at three time-points: (i) acute phase prior to treatment, (ii) subacute phase and (iii) convalescent phase. Myeloid DC (mDC), but not plasmacytoid DC (pDC), were numerous in the peripheral blood in acute KD subjects and decreased in the subacute phase in both IVIG⁻ and IVIG ⁺ infliximab-treated groups. The co-stimulatory molecule for antigen presentation to T cells and CD86 decreased in mDC from acute to subacute time-points in both treatment groups, but not in the single patient who developed coronary artery aneurysms. We also defined tolerogenic mDC that expand in the subacute phase of KD not impaired by infliximab treatment. T_reg and T_mem expanded after treatment with no significant differences between the two groups. Treatment of KD patients with infliximab does not adversely affect generation of tolerogenic mDC or the development of T cell regulation and memory.     

小儿川崎病CD4+T细胞CD40L和E-选择素的表达

目的：通过检测川崎病患儿静脉输注丙球治疗前后外周血T细胞表面CD40L（CD154）表达,探讨川崎病冠状动脉损伤的发病机制.方法：采用流式细胞仪检测26例川崎病患儿静脉输注丙球治疗前后、16例其他发热性疾病患儿、15例正常儿童外周血T细胞表面的CD40L表达.采用酶联免疫吸附试验检测相应血清中可溶性CD40L（sCD40L） 及E-选择素.结果：川崎病患儿CD4^＋T细胞表面CD40L表达及血清中E-选择素显著高于其他发热性疾病对照组及正常儿童对照组（P＜0.01）,川崎病患儿静脉输注丙球治疗后明显下降（P＜0.01）.CD4^＋T细胞表面CD40L表达及E-选择素与川崎病冠状动脉损伤有关,而CD8^＋T细胞表面CD40L的表达及可溶性CD40L与冠状动脉损伤无明显相关性.川崎病患儿CD4^＋T细胞表面CD40L表达与E-选择素水平正相关（r=0.626,P＜0.05）.结论：CD40L异常表达及血清中E-选择素在川崎病发病机制中起重要作用.静脉输注丙球能下调CD40L表达及血清中E-选择素,且有利于治疗血管炎.     

Association between Adipokines and Coronary Artery Lesions in Children with Kawasaki Disease

Body fat is an important source of adipokine, which is associated with energy balance and inflammatory and immune responses. However, the role of adipokines in coronary artery complications in Kawasaki disease (KD) has not yet been fully explained. We investigated whether serum adipokine level can be a useful marker for patients with KD who are at higher risk of developing coronary artery lesion (CAL). We measured adipokine levels and other inflammatory parameters in 40 patients with KD, 32 febrile controls, and 15 afebrile controls. Interleukin (IL)-6, tumor necrosis factor (TNF)-α and other laboratory parameters were also measured before and after intravenous immunoglobulin therapy, and in the convalescent phase. At admission, the serum resistin levels in KD children were significantly higher than those in controls (177.56 ng/mL in KD children, 76.48 ng/mL in febrile controls, and 17.95 ng/mL in afebrile controls). In patients with KD, resistin levels were significantly associated with decreased hemoglobin levels (P=0.049) and increased IL-6 levels (P=0.014). The serum IL-6 levels were significantly higher and body mass index was significantly lower in the group of KD with CALs than those without CALs (228.26 ng/mL vs. 39.18 ng/mL and 15.09 vs. 16.60, respectively). In conclusion, resistin is significantly elevated in KD patients, although it has no prognostic value of predicting coronary artery lesion in the acute stage.

Graphical Abstract

相似文献   

Lack of Association between ORAI1/CRACM1 Gene Polymorphisms and Kawasaki Disease in the Taiwanese Children

Objective

Kawasaki disease (KD) is characterized by systemic vasculitis of an unknown cause. A previous study has indicated that a polymorphism of the inositol 1,4,5-trisphosphate 3-kinase C (ITPKC) gene is involved in the susceptibility to KD. ORAI (also known as CRACM1) is one of the components of store-operated calcium channels involved in regulating immune and inflammatory reactions. This study was conducted to investigate if polymorphisms in ORAI1/CRACM1, a gene downstream from ITPKC, are associated with KD susceptibility and clinical outcomes.

Materials and Methods

A total of 1,056 subjects (341 KD patients and 715 controls) were investigated to identify five tagging single nucleotide polymorphisms (tSNPs) in ORAI1/CRACM1 (rs12313273, rs6486795, rs7135617, rs12320939, and rs712853) by using the TaqMan Allelic Discrimination assay.

Results

No significant associations between genotype and allele frequency of the five ORAI1/CRACM1 tSNPs were observed in the KD patients and controls. In KD patients, no significant associations between ORAI1/CRACM1 polymorphisms and coronary artery lesion (CAL) formation or intravenous immunoglobulin (IVIG) treatment response were observed. The results from haplotype analysis were insignificant.

Conclusions

This study showed for the first time that ORAI1/CRACM1 polymorphisms are not associated with KD susceptibility, CAL formation, or IVIG treatment response in the Taiwanese population.     

儿童再发川崎病77例临床特征回顾性分析

目的探讨再发川崎病（KD）的临床特点及其预后。方法收集1994年1月至2012年10月重庆医科大学附属儿童医院收治的KD再发病例,比较初发时和复发时的临床特征、实验室指标和随访资料。并选取5～10年未再发KD病例作为对照组,探讨KD再发可能的危险因素。结果19年间收治KD4875例,其中再发KD77例,再发1次74例,再发2次3例,男：女为1．4：1。再发平均间隔时间1．6年,1年以内再发45．4％（35／77）。发热病程再发时较初发时缩短（7．6±3．1）vs（8．9±3．8）d,P〈0．05;WBC和CRP水平再发时较初发时显著降低,（14．3±5．7）vs（16．2±5．4）×10^9·L^-1和（61±58）vs（95±76）mg·L^-1,P均〈0．05。急性期（病程≤30d）冠状动脉病变（CAL）发生率初发时为17．8％（13／73）,再发时为13．3％（10／75）;应用IVIG后亚急性期（病程〉30d）CAL发生率初发时为11．O％（8／73）,再发时为9．3％（7／75）,组间比较差异均无统计学意义。7例初发时与再发时均有CAL,其中l例初发时与再发时均合并冠状动脉瘤（CAA）。52例KD再发患儿有出院后随访资料,随访时间平均2．1年,其中1例再发时合并左侧冠状动脉主干小型CAA的患儿随访中出现新发部位左前降支瘤样扩张,冠状动脉内径回缩至正常后4年7个月再次出现左侧冠状动脉扩张。多因素Logistic分析显示,年龄〈3岁、性别、热程〉10d、并发CAL及WBC〉20×10^9·L^-1均与KD再发无统计学关联。结论KD再发多发生在1年内。再发KD的CAL总发生率并未升高,初发时合并CAL患儿,再发时更易发生CAL。     

IL-12B 基因rs3212227位点多态性与川崎病及其并发冠状动脉损伤的关联性研究

目的：探讨IL-12B 基因rs3212227位点多态性与川崎病（KD）及其并发冠状动脉损伤（CAL）的关联性。方法：收集2004年至2014年间83例KD患儿及86例健康儿童外周血标本,提取DNA,应用基因扩增－聚合酶链限制性长片段法（PCR-RFLP）检测IL-12B 基因rs3212227位点多态性,并用直接测序法进行验证;χ2检验分析该位点多态性与KD及其并发CAL之间是否存在关联性,P<0.05代表差异有统计学意义。结果：KD组AA、AC、CC基因型分布和A、C等位基因分布与对照组比较差异无统计学意义（χ²=4.095、3.31,P>0.05）。KD组中合并CAL组基因型和等位基因分布与冠状动脉正常组（NCAL组）比较差异亦无统计学意义（χ²=1.586、1.254,P>0.05）。结论：IL-12B 基因rs3212227位点多态性与川崎病及其并发冠状动脉损伤有关联。     

Epidemiologic study of Kawasaki disease and cases resistant to IVIG therapy in Thailand

The incidence of Kawasaki disease (KD) in Thailand has never been studied before. We reviewed the data from the National Registry of Thai Children who had KD between 1998-2002 to evaluate the incidence of KD and cases resistant to treatment with intravenous immunoglobulin (IVIG). Resistance to IVIG was defined as remaining febrile at least 48 hours after initial IVIG therapy. There were 710 KD patients in the registry. The incidence of KD was from 2.14 to 3.43 cases per 100,000 children aged 0-5 years. During the acute phase 15.6% of 435 patients were considered as resistant cases. Resistant cases of KD in Thai children are quite common (15.6%) even after IVIG treatment. We found that patients who had high white blood cell counts (> 16,500 cells/mm3) had a higher likelihood of being resistant.     

Kawasaki disease: laboratory findings and an immunopathogenesis on the premise of a "protein homeostasis system"

Kawasaki disease (KD) is a self-limited systemic inflammatory illness, and coronary artery lesions (CALs) are a major complication determining the prognosis of the disease. Epidemiologic studies in Asian children suggest that the etiologic agent(s) of KD may be associated with environmental changes. Laboratory findings are useful for the diagnosis of incomplete KD, and they can guide the next-step in treatment of initial intravenous immunoglobulin non-responders. CALs seem to develop in the early stages of the disease before a peak in inflammation. Therefore early treatment, before the peak in inflammation, is mandatory to reduce the risk of CAL progression and severity of CALs. The immunopathogenesis of KD is more likely that of acute rheumatic fever than scarlet fever. A hypothetical pathogenesis of KD is proposed under the premise of a "protein homeostasis system"; where innate and adaptive immune cells control pathogenic proteins that are toxic to host cells at a molecular level. After an infection of unknown KD pathogen(s), the pathogenic proteins produced from an unknown focus, spread and bind to endothelial cells of coronary arteries as main target cells. To control the action of pathogenic proteins and/or substances from the injured cells, immune cells are activated. Initially, non-specific T cells and non-specific antibodies are involved in this reaction, while hyperactivated immune cells produce various cytokines, leading to a cytokine imbalance associated with further endothelial cell injury. After the emergence of specific T cells and specific antibodies against the pathogenic proteins, tissue injury ceases and a repair reaction begins with the immune cells.     

Imbalance in the production between vascular endothelial growth factor and endostatin in Kawasaki disease

To investigate whether an imbalance exists in the production between angiogenic and antiangiogenic growth factors in patients with Kawasaki disease (KD), we measured the serum levels of vascular endothelial growth factor (VEGF) and endostatin (ES) in 35 patients with KD, 15 patients with acute febrile diseases (disease controls) and 15 healthy children. KD patients had significantly higher VEGF levels and lower ES levels (P < 0.01) in the acute and subacute phases than the disease control and healthy children. KD patients with coronary artery lesions (CAL, n = 10) had significantly higher VEGF levels and lower ES levels (P < 0.05) in the subacute and convalescent phases than those without CAL (n = 25). The ratios of VEGF/ES in sera of KD patients with CAL were significantly higher (P < 0.05) in the acute and convalescent phases compared to those without CAL. Furthermore, the occurrence of CAL significantly correlated with the VEGF/ES ratio above 10 x 10(-3) in the subacute phase of KD (Odds ratio 17.25, P = 0.005). The findings in the present study indicate that an imbalance exists in the production between VEGF and ES in patients with KD while also suggesting that KD patients with a high VEGF/ES ratio have a significantly greater risk of CAL involvement.     

急性期川崎病Th17细胞变化初探

目的 探讨Th17细胞在川崎病(Kawasaki disease,KD)免疫发病机制中的作用.方法 急性期KD患儿60例,正常同年龄对照组32例,KD患儿分别于静脉丙种球蛋白(IVIG)治疗前后直接取血备检.采用荧光定量PCR(real-time PCR)检测CD4+T细胞IL-17A/F、转录因子ROR-γt、Foxp3及PBMC IL-6、TGF-β、IL-23p19、IL-27p28、IL-27EBI3、IFN-γ等mRNA表达;酶联免疫吸附试验检测血浆中IL-6、TGF-β、IL-23、IL-27、IFN-γ的蛋白浓度;流式细胞术检测外周血CD4+CD25+调节性T细胞(Tr)的比例.结果 急性期KD患儿CD4+T细胞高表达IL-17A及IL-17F(P<0.01),IVIG治疗后明显降低(P<0.01);急性期KD患儿IL-17A/IL-17F与红细胞沉降率(ESR)、C反应蛋白(CRP)、白细胞数目(WBC)呈正相关(IL-17A:0.70,0.85,0.80,P<0.01;IL-17F:0.63,0.65,0.69,P<0.01);急性期KD患儿Th17细胞转录因子ROR-γt及前炎症细胞因子IL-6转录水平明显高于对照组(P<0.01),IVIG治疗后显著降低(P<0.01);TGF-β、IL-23p19、IL-27p28、IL-27EBI3 mRNA水平及血浆蛋白浓度与对照组比较差异无统计学意义(P>0.05);血浆IFN-γ浓度显著升高,mRNA水平无变化;急性期KD患儿CD4+ CD25+ Tr细胞比例明显低于正常对照组(P<0.01),其转录因子Foxp3表达亦明显降低(P<0.01).结论 急性期KD患儿Th17细胞过度活化可能参与了KD免疫发病机制.     

Polymorphism of Fcγ RIIa May Affect the Efficacy of γ-Globulin Therapy in Kawasaki Disease

We evaluated whether there is a possible relationship between the effectiveness of γ-globulin treatment for patients with Kawasaki disease (KD) and the polymorphism of Fcγ RIIa, IIIb, and IIIa. Genomic DNA was extracted from whole blood collected from 56 patients with KD who received γ-globulin treatment. The genotypes for Fcγ RIIIb-NA(1, 2), Fcγ RIIa-H/R131, and FcγRIIIa-F/V158 were determined to investigate the association between these polymorphisms and the development of coronary lesions (CALs). Twenty-three percent of patients with the HH allele for the Fcγ RIIa polymorphism progressed to CALs, compared with 60% with the HR and RR alleles. HR and RR alleles may be a predictor of the progression of CALs in KD before the initiation of γ-globulin therapy.     

CASP3 gene single-nucleotide polymorphism (rs72689236) and Kawasaki disease in Taiwanese children

Kawasaki disease (KD) is characterized by systemic vasculitis of unknown etiology. A study from Japan reported that G to A substitution of a single-nucleotide polymorphism (SNP) located in the 5'-untranslated region of caspase 3 (CASP3) (rs72689236), which was associated with nuclear factor of activated T cell-mediated T-cell activation, is responsible for susceptibility to KD. This study was conducted to investigate whether the polymorphism of CASP3 is responsible for susceptibility and coronary artery lesion (CAL) formation in KD in the Taiwanese population. A total of 1092 subjects (341 KD patients and 751 controls) were investigated to identify an SNP of rs72689236 using Invader assays (Third Wave Technologies). Our data provided a borderline significant association between the genotypes and allele frequency of rs72689236 in control subjects and KD patients (P=0.0535 under the dominant model; P=0.0575 under the allelic model). The A allele of rs72689236 in KD patients and in patients with CAL and intravenous immunoglobulin resistance was seen in a higher frequency. Importantly, a significant association was obtained between rs72689236 and KD patients with aneurysm formation (P=0.009, under the recessive model). The A allele of rs72689236 is very likely to be a risk allele in the development of aneurysm in patients with KD.