TY - JOUR
T1 - Desmoglein-Specific B-Cell−Targeted Single-Cell Analysis Revealing Unique Gene Regulation in Patients with Pemphigus
AU - Egami, Shohei
AU - Watanabe, Takashi
AU - Fukushima-Nomura, Ayano
AU - Nomura, Hisashi
AU - Takahashi, Hayato
AU - Yamagami, Jun
AU - Ohara, Osamu
AU - Amagai, Masayuki
N1 - Funding Information:
The authors thank Prof John R. Stanley for his critical and constructive guidance for this project. We are also grateful to Yoshiki Mochizuki for his technical assistance and Mariko Okajima (Keio University) for laboratory management. This work was supported by Grants-in-Aid for Scientific Research (S) Grant Number JP21229014 , JP17109012 (to MA), and (A) Grant Number JP26253065 (to MA), JP19H01051 (to HT) from the Ministry of Education, Culture, Sports, Science, and Technology of Japan .
Funding Information:
The authors thank Prof John R. Stanley for his critical and constructive guidance for this project. We are also grateful to Yoshiki Mochizuki for his technical assistance and Mariko Okajima (Keio University) for laboratory management. This work was supported by Grants-in-Aid for Scientific Research (S) Grant Number JP21229014, JP17109012 (to MA), and (A) Grant Number JP26253065 (to MA), JP19H01051 (to HT) from the Ministry of Education, Culture, Sports, Science, and Technology of Japan. Conceptualization: SE, JY, MA; Formal Analysis: TW, AFN; Funding Acquisition: JY, MA; Investigation: SE, TW, HN; Methodology: SE, TW; Supervision: JY, OO, MA; Writing – Original Draft Preparation: SE; Writing – Review and Editing: JY, HT, OO, MA
Publisher Copyright:
© 2023 The Authors
PY - 2023
Y1 - 2023
N2 - Autoreactive B cells are assumed to play a critical role in pemphigus; however, the characteristics of these cells are not yet fully understood. In this study, 23 pemphigus vulgaris or pemphigus foliaceus samples were used to isolate circulating desmoglein (DSG)-specific B cells. Transcriptome analysis of the samples was performed at the single-cell level to detect genes involved in disease activity. DSG1- or DSG3-specific B cells from three patients’ differentially expressed genes related to T cell costimulation (CD137L) as well as B-cell differentiation (CD9, BATF, TIMP1) and inflammation (S100A8, S100A9, CCR3), compared with nonspecific B cells from the same patients. When the DSG1-specific B cells before and after treatment transcriptomes of the patient with pemphigus foliaceus were compared, there were changes in several B-cell activation pathways not detected in non−DSG1-specific B cells. This study clarifies the transcriptomic profile of autoreactive B cells in patients with pemphigus and documents the gene expression related to disease activity. Our approach can be applied to other autoimmune diseases and has the potential for future detection of disease-specific autoimmune cells.
AB - Autoreactive B cells are assumed to play a critical role in pemphigus; however, the characteristics of these cells are not yet fully understood. In this study, 23 pemphigus vulgaris or pemphigus foliaceus samples were used to isolate circulating desmoglein (DSG)-specific B cells. Transcriptome analysis of the samples was performed at the single-cell level to detect genes involved in disease activity. DSG1- or DSG3-specific B cells from three patients’ differentially expressed genes related to T cell costimulation (CD137L) as well as B-cell differentiation (CD9, BATF, TIMP1) and inflammation (S100A8, S100A9, CCR3), compared with nonspecific B cells from the same patients. When the DSG1-specific B cells before and after treatment transcriptomes of the patient with pemphigus foliaceus were compared, there were changes in several B-cell activation pathways not detected in non−DSG1-specific B cells. This study clarifies the transcriptomic profile of autoreactive B cells in patients with pemphigus and documents the gene expression related to disease activity. Our approach can be applied to other autoimmune diseases and has the potential for future detection of disease-specific autoimmune cells.
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U2 - 10.1016/j.jid.2023.03.1661
DO - 10.1016/j.jid.2023.03.1661
M3 - Article
C2 - 36997112
AN - SCOPUS:85153877551
SN - 0022-202X
JO - Journal of Investigative Dermatology
JF - Journal of Investigative Dermatology
ER -