35097 Characterization of B cell dynamics in hidradenitis suppurativa: Evidence for antigen-driven pathophysiology

Abstract

Hidradenitis suppurativa (HS) is a high-morbidity, chronic inflammatory skin disorder that affects an estimated 1% of adults in developed countries and is disproportionately prevalent among African Americans and women. Lesions in HS primarily affect intertriginous sites and present as painful inflammatory nodules, subcutaneous abscesses, and scarring subcutaneous tunnels. Histologically, these lesions are rich in inflammatory infiltrate including T cells, neutrophils, macrophages, dendritic cells, B cells and plasma cells. While the role of B cells and their late differentiation partner, plasma cells, are unclear in HS, emerging evidence has suggested a link between these cells, disease progression, and treatment response. Here, we further characterize B cells in HS using single cell RNA-seq (scRNA-seq) and bacteriophage immunoprecipitation sequencing (PhIP-seq) to identify local and global alterations to B cell and plasma cell populations in HS. Using published bulk RNA-seq data from HS lesions and control skin, we extracted CDR3 sequences using MiXCR software. Diversity analysis demonstrated an increase in clonotypes in HS skin compared with control skin (P < .05). Further analysis of clonal populations in HS skin using D50 diversity index revealed selective clonal expansions (P < .01). To understand whether B cell axis alterations in HS were limited to the lesion, we assayed serum from 10 HS patients and 14 controls using PhIP-seq. HS patients possessed serum autoreactivity to a set of four autoantigens compared with controls, including type I collagen (P < .01 for each). Together, these studies provide evidence for local and global alteration to B cell populations in an antigen-specific manner in HS.