Gene expression profiling and multiplex immunofluorescence analysis of bullous pemphigoid immune-related adverse event reveal upregulation of toll-like receptor 4/complement-induced innate immune response and increased density of T H 1 T-cells

Immune checkpoint inhibitor (ICI)-based cancer therapies cause a variety of cutaneous immune-related adverse events (irAEs) including immunobullous skin eruptions like bullous pemphigoid (BP). However, little is known about the underlying immunopathogenic drivers of these reactions, and understandin...

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Published in:Journal of cutaneous pathology 2023-07, Vol.50 (7), p.661-673
Main Authors: Marques-Piubelli, Mario L, Seervai, Riyad N H, Mudaliar, Kumaran M, Ma, Wencai, Milton, Denái R, Wang, Jing, Muhlbauer, Aaron, Parra, Edwin R, Solis, Luisa M, Nagarajan, Priyadharsini, Speiser, Jodi, Hudgens, Courtney, Cho, Woo Cheal, Aung, Phyu P, Patel, Anisha, Pacha, Omar, Nelson, Kelly C, Tetzlaff, Michael T, Amaria, Rodabe N, Torres-Cabala, Carlos A, Prieto, Victor G, Wistuba, Ignacio I, Curry, Jonathan L
Format: Article
Language:English
Subjects:
Blister - metabolism
Complement System Proteins
Fluorescent Antibody Technique
Gene Expression Profiling
Humans
Immunity, Innate
Pemphigoid, Bullous - pathology
RNA, Messenger
Toll-Like Receptor 4 - metabolism
Up-Regulation
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Summary:Immune checkpoint inhibitor (ICI)-based cancer therapies cause a variety of cutaneous immune-related adverse events (irAEs) including immunobullous skin eruptions like bullous pemphigoid (BP). However, little is known about the underlying immunopathogenic drivers of these reactions, and understanding the unique gene expression profile and immune composition of BP-irAE remains a critical knowledge gap in the field of oncodermatology/oncodermatopathology. BP-irAE (n = 8) and de novo BP control (n = 8) biopsy samples were subjected to gene expression profiling using the NanoString® Technologies nCounter PanCancer Immune Profiling Panel. Multiplex immunofluorescence (mIF) studies using markers for T-cells (CD3 and CD8), T helper 1 (T 1) cells (Tbet), T 2 cells (Gata3), T 17 cells (RORγT), and regulatory T-cells (Tregs; FoxP3) were further evaluated using InForm® image analysis. Compared with de novo BP controls, BP-irAE samples exhibited upregulation of 30 mRNA transcripts (p 
ISSN:0303-6987
1600-0560
DOI:10.1111/cup.14442