Immunophenotypic and Transcriptomic Analysis of Peripheral Blood Mononuclear Cells in Bullous Pemphigoid
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Background: Bullous pemphigoid (BP) is an autoimmune blistering disease driven by auto- antibodies against BP180 and BP230. While type 2 inflammation plays a key role, the precise immune cell alterations and transcriptomic changes remain unclear. Objective: To characterize immune cell composition and transcriptomic changes in BP patients using fluorescence-activated cell sorting (FACS)-based immunophenotyping and RNA sequencing. Methods: A case-control study was conducted on 10 newly diagnosed, treatment-naive BP patients and six healthy controls. Disease activity was assessed using the Bullous Pemphigoid Disease Area Index (BPDAI). Peripheral blood mononuclear cells were isolated for FACS anal- ysis to determine immune cell subsets. RNA sequencing was performed to identify differen- tially expressed genes (DEGs) and enriched pathways. Statistical analyses included t-tests, Mann-Whitney U tests, and correlation analysis. Results: FACS analysis revealed a reduction in CD4 T cells, T helper 2 (Th2), and B cells in BP patients (p<0.05), alongside an increase in M2a-like monocytes (p<0.001). RNA sequencing identified 262 DEGs, with secretory leukocyte peptidase inhibitor (SLPI) and transmembrane protein 237 being the most significantly upregulated. 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). Gene ontology analysis highlighted enrichment in inflammatory responses and neutrophil degranulation pathways. Conclusion: BP patients show distinct immune dysregulation, including decreased CD4 T cells, Th2, and B cells, increased M2a-like monocytes, altered gene expression profiles, and correla- tions between PSTPIP2, SAMSN1 and disease activity. These findings provide insights into pathogenesis and potential therapeutic targets of BP.
Abstract
Background: Bullous pemphigoid (BP) is an autoimmune blistering disease driven by auto- antibodies against BP180 and BP230. While type 2 inflammation plays a key role, the precise immune cell alterations and transcriptomic changes remain unclear. Objective: To characterize immune cell composition and transcriptomic changes in BP patients using fluorescence-activated cell sorting (FACS)-based immunophenotyping and RNA sequencing. Methods: A case-control study was conducted on 10 newly diagnosed, treatment-naive BP patients and six healthy controls. Disease activity was assessed using the Bullous Pemphigoid Disease Area Index (BPDAI). Peripheral blood mononuclear cells were isolated for FACS anal- ysis to determine immune cell subsets. RNA sequencing was performed to identify differen- tially expressed genes (DEGs) and enriched pathways. Statistical analyses included t-tests, Mann-Whitney U tests, and correlation analysis. Results: FACS analysis revealed a reduction in CD4 T cells, T helper 2 (Th2), and B cells in BP patients (p<0.05), alongside an increase in M2a-like monocytes (p<0.001). RNA sequencing identified 262 DEGs, with secretory leukocyte peptidase inhibitor (SLPI) and transmembrane protein 237 being the most significantly upregulated. 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). Gene ontology analysis highlighted enrichment in inflammatory responses and neutrophil degranulation pathways. Conclusion: BP patients show distinct immune dysregulation, including decreased CD4 T cells, Th2, and B cells, increased M2a-like monocytes, altered gene expression profiles, and correla- tions between PSTPIP2, SAMSN1 and disease activity. These findings provide insights into pathogenesis and potential therapeutic targets of BP.