Kawasaki Disease Center, Kaohsiung Chang Gung Memorial Hospital.
Department of Pediatrics, Kaohsiung Chang Gung Memorial Hospital and Chang Gung University College of Medicine.
Circ J. 2019 Sep 25;83(10):2070-2078. doi: 10.1253/circj.CJ-19-0206. Epub 2019 Aug 3.
Kawasaki disease (KD) severely threatens young children's health worldwide. The pathogenic mechanism of KD has not yet been solved, so there is still debate over whether KD is an infectious disease or an autoimmune disease.
To solve this problem, an immune repertoire analysis of KD was conducted. We collected blood cell RNA samples and prepared them into amplicons with iRepertoire kits. The amplicons were sequenced and analyzed with the iRepertoire pipeline. We first identified KD-specific VJ and VDJ forms that had the potential to serve as biomarkers of KD. In addition, the KD-specific VDJ forms were contributed mostly by immunoglobulin G. The D50 value analysis showed that B-cell diversity in KD is decreased, suggesting unique immunoglobulins are produced in KD. Moreover, V, D and J segment usage in IgA, IgG and IgM was consistent with previous KD studies. Further comparison showed no difference in CDR3 peptide length between KD and fever controls (subjects with fever but not diagnosed as KD), indicting KD had B-cell selection phenomenon that has a non-autoimmune pattern. The comparison of amino acid usage of the CDR3 region demonstrated a preference for hydrophilic amino acids in KD.
The results of D50 value, VDJ usage and CDR3 peptide length analyses suggested the characteristics of infectious disease for KD.
川崎病(KD)严重威胁着全世界儿童的健康。KD 的发病机制尚未解决,因此关于 KD 是传染病还是自身免疫性疾病仍存在争议。
为了解决这个问题,我们对 KD 进行了免疫受体库分析。我们收集了血液细胞 RNA 样本,并使用 iRepertoire 试剂盒将其制备成扩增子。使用 iRepertoire 管道对扩增子进行测序和分析。我们首先确定了 KD 特异性的 VJ 和 VDJ 形式,它们有可能成为 KD 的生物标志物。此外,KD 特异性的 VDJ 形式主要由免疫球蛋白 G 贡献。D50 值分析表明,KD 中的 B 细胞多样性降低,提示 KD 中产生了独特的免疫球蛋白。此外,IgA、IgG 和 IgM 中的 V、D 和 J 片段使用与之前的 KD 研究一致。进一步的比较表明,KD 与发热对照组(发热但未被诊断为 KD 的患者)之间的 CDR3 肽长度没有差异,表明 KD 存在 B 细胞选择现象,具有非自身免疫模式。CDR3 区氨基酸使用的比较表明,KD 中亲水氨基酸偏好。
D50 值、VDJ 使用和 CDR3 肽长度分析的结果表明 KD 具有传染病的特征。