Immunophenotypic and Transcriptomic Analysis of Peripheral Blood Mononuclear Cells in Bullous Pemphigoid

Area of Science:

• Immunology
• Dermatology
• Genomics

Background:

• Bullous pemphigoid (BP) is an autoimmune blistering disease characterized by autoantibodies against BP180 and BP230.
• Type 2 inflammation is implicated, but specific immune cell alterations and transcriptomic changes in BP are not fully understood.

Purpose of the Study:

• To comprehensively characterize immune cell composition and transcriptomic profiles in treatment-naive bullous pemphigoid patients.
• To identify key immune dysregulations and potential molecular markers associated with disease activity.

Main Methods:

• A case-control study involving 10 newly diagnosed BP patients and 6 healthy controls.
• Fluorescence-activated cell sorting (FACS) for immunophenotyping and RNA sequencing for transcriptomic analysis.
• Disease activity assessed using the Bullous Pemphigoid Disease Area Index (BPDAI).

Main Results:

• FACS revealed decreased CD4+ T cells, T helper 2 (Th2) cells, and B cells, with increased M2a-like monocytes in BP patients (p<0.05).
• RNA sequencing identified 262 differentially expressed genes (DEGs), including upregulated secretory leukocyte peptidase inhibitor (SLPI) and transmembrane protein 237.
• Proline-serine-threonine phosphatase interacting protein 2 (PSTPIP2) and SAM domain, SH3 domain, and nuclear localization signals 1 (SAMSN1) positively correlated with BPDAI (p<0.001).

Conclusions:

• Bullous pemphigoid patients display significant immune dysregulation, including specific alterations in T cell, B cell, and monocyte populations.
• Altered gene expression profiles, particularly PSTPIP2 and SAMSN1, correlate with disease severity, suggesting roles in BP pathogenesis.
• These findings highlight potential therapeutic targets for bullous pemphigoid.