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ORIGINAL RESEARCH article

Front. Immunol.
Sec. Autoimmune and Autoinflammatory Disorders : Autoimmune Disorders
Volume 15 - 2024 | doi: 10.3389/fimmu.2024.1438640
This article is part of the Research Topic Mechanism and Precise Therapy of Immune-Mediated Diseases in Pediatrics View all 6 articles

The Mechanism underlying B cell Developmental Dysfunction in Kawasaki Disease Based on Single-cell Transcriptomic Sequencing

Provisionally accepted
秋萍 林 秋萍 林 1Zhen Wang Zhen Wang 2Guohui Ding Guohui Ding 3Guang Li Guang Li 4Liqin Chen Liqin Chen 1Qingzhu Qiu Qingzhu Qiu 1Sirui Song Sirui Song 1Wei Liu Wei Liu 1Xunwei Jiang Xunwei Jiang 1Min Huang Min Huang 1Libing Shen Libing Shen 3Tingting Xiao Tingting Xiao 1Lijian Xie Lijian Xie 3*
  • 1 Shanghai Children's Hospital, Shanghai, Shanghai Municipality, China
  • 2 Shanghai Institute of Nutrition and Health, Chinese Academy of Sciences (CAS), Shanghai, Shanxi Province, China
  • 3 International Human Phenome Institutes (Shanghai), Shanghai, China
  • 4 Independent researcher, Shanghai, China

The final, formatted version of the article will be published soon.

    Kawasaki disease (KD) is an acute systemic vasculitis that can lead to acquired heart disease in children mostly from in developed countries. The previous research showed that B cells in KD patients underwent a profound change in both the cell numbers and types after intravenous immunoglobulin (IVIG) therapy. We performed the single-cell RNA-sequencing for the peripheral blood mononuclear cells (PBMCs) from three febrile patients and three KD patients to investigate the possible mechanism underlying B cell developmental dysfunction in KD. Overall single-cell expression profiles show that the biological processes of immunity, B cell activation pathway and their related biological entities are repressed in KD patients before IVIG treatment compared to febrile patient and KD patients after IVIG treatment. The differentially expressed gene analyses further demonstrate that B cell signaling pathway is downregulated in B cells and plasma blast cells of KD patients before treatment while cell cycle genes and MYC gene are upregulated in dendritic cells (DCs) and hematopoietic stem and progenitor cells (HSPCs) of KD patients before treatment. The biological process of immune response is upregulated in the HSPCs of KD patients before treatment in our dataset while the biological process of inflammatory response is upregulated in the HSPCs of KD patients before treatment in GSE168732 dataset. Single-cell trajectory analyses demonstrate that KD patients before treatment have a shortened developmental path in which B cells and T cells are failed to differentiate into separate lineages. HSPD1 and HSPE1 genes show an elevated expression level in the early cell development stage of KD patients before treatment accompanied with the repression of MYC, SPI1, MT2A and UBE2C genes. Our analyses of all B cells from KD patients before treatment show most of B cells are arrested in a transitional state with an ill developmental path compared with febrile patients and KD patients after treatment. Our results indicate that the immune premature HSPCs accompanied with the abnormal expression dynamics of cell cycle and SPI1 genes are the mechanism underlying B cell developmental dysfunction in KD patients.

    Keywords: kawasaki disease, single-cell transcriptomic sequencing, B cell Developmental Dysfunction, HSPD1, HSPE1, MYC, SPI1

    Received: 26 May 2024; Accepted: 27 Sep 2024.

    Copyright: © 2024 林, Wang, Ding, Li, Chen, Qiu, Song, Liu, Jiang, Huang, Shen, Xiao and Xie. This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) or licensor are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.

    * Correspondence: Lijian Xie, International Human Phenome Institutes (Shanghai), Shanghai, China

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