Desmoglein-Specific B-Cell−Targeted Single-Cell Analysis Revealing Unique Gene Regulation in Patients with Pemphigus

• Published in: Journal of investigative dermatology Vol. 143; no. 10; pp. 1919 - 1928.e16
• Main Authors: Egami, Shohei, Watanabe, Takashi, Fukushima-Nomura, Ayano, Nomura, Hisashi, Takahashi, Hayato, Yamagami, Jun, Ohara, Osamu, Amagai, Masayuki
• Format: Journal Article
• Language: English
• Published: United States Elsevier Inc 01.10.2023
• Subjects: PV; DEG; His-tag; MBC; mcPV; BCR; E-tag; mPV; rDSG; VH; 7AAD; APC; PPAR; RNA-seq; PF; DSG; HA; HC; IPA
• ISSN: 0022-202X; 1523-1747
• DOI: 10.1016/j.jid.2023.03.1661

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.