Abstract
"川崎病（KD）為兒童後天性心臟病的最常見原因，是一種急性血管炎，伴有發燒，淋巴結紅腫和皮膚粘膜表現等綜合表現疾病。大約60年前由日本的川崎博士在日本發表第一份對川崎症的報告以來，川崎病的病因學目前仍是不明，且台灣地區每年每10萬名5歲以下兒童的發病率為50至70人，遠高於西方國家，僅次於日本和韓國，為世界第三高。川崎症致冠狀動脈血管瘤有7.3% (536/7305)，且少部份病人會有復發川崎症之機會，約1.3% (94/7305)。因此，川崎病被認為是台灣最重要的兒童疾病之一，然而，缺乏特異性的診斷測試，其免疫發病機制仍不清楚。為了改善早期診斷和結果，必須對免疫病理，診斷和治療策略進行深入研究。
而最新的研究顯示，川崎病為多種因素引起的；並且在感染後造成過度活化的宿主基因表現，如BLK及CD40已知可能為川崎症的易感性致病基因。加上主持人先前研究也發現川崎症病人的糞便微菌叢有其特異性。結合上述之種種，本試驗提出在結合宿主免疫基因表現及分析B細胞受器資料庫序列分析研究川崎病的免疫發病機理；而微菌叢和B細胞調節之間的相互作用可能在川崎病的免疫發病機制中起重要作用，本試驗涵蓋上述將可深入研究川崎氏症病人身上的專一性抗體，於將來可用於早期診斷川崎氏症甚或治療的方法。"
" Kawasaki disease, the most common cause of acquired heart diseases in children, is an acute vasculitis with a syndromic constellation of fever, lymphadenopathy, and mucocutaneous manifestations. KD is caused by multiple factors, including various heterogeneous infections, significance of host gene expression. Given that BLK and CD40L polymorphisms were associated with KD susceptibility, and that BLK and CD40L are related to immune regulation, especially in B cell regulation. Further, robust evidence supports microbiome modulation of the mucosal immune system, but the connection between the microbiome and KD has rarely been explored.
We thus proposed that the aberrant interplay between the microbiota and B cell regulation may play an important role in the immunopathogenesis of KD. Therefore, we aim to investigate the B cell immune repertoires, their specific diverse sequences and antibody production as well as respiratory/intestinal microbiota in KD cases. We also plan to explore the contributions of the interplay between B cells and microbiota to the occurrence of coronary arterial lesions in KD cases.
We will enroll KD cases and collect stool/respiratory specimens and blood samples, as well as to collect serial detailed follow up of coronary arterial conditions and analyze gut and respiratory microbiota to find specific microbiota associated with KD and coronary arterial dilatation at the species level with 16s rRNA sequencing. We will also identify the microbiota causing the altered distribution of blood B cell subsets, particular Bregs, in KD and identify the altered B cell repertoires and antibodies in KD, and test if the identified antibodies recognize endothelial cells or microbiota. The anti-inflammatory or inflammatory activity of the specific taxonomy on the endothelial cells will also be clarified.
We expect that significant microbiota and B cell immune repertoires associated with KD and coronary arterial dilatation will be identified, which have been an unexplored research area and will lead to a new research direction. Results from this study can be used as a biomarker, treatment or prevention strategy for KD and the related coronary arterial lesions. Particularly, dysbiotics identified by this project may be developed as a novel treatment target for KD.
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Keyword(s)
川崎氏症
冠狀動脈病變
B細胞免疫反應
微菌叢
Kawasaki disease
coronary arterial dilation
B cell immune
microbiota
