Unique B- and plasma cell signature differentiates hidradenitis suppurativa from psoriasis and atopic dermatitis

Introduction: Hidradenitis suppurativa (HS), psoriasis (PsO), and atopic dermatitis (AD) have unique disease pathogenesis and distinct pathology, despite sharing some immunological pathways. This study aimed to evaluate the transcriptomic differences between HS, PsO, and AD lesions, which drive these unique pathogenic features. Methods: Bulk RNA sequencing was performed on 19 healthy controls (HC), 15 HS, 21 PsO, and 15 AD lesional skin samples. Results: PsO lesions were defined by a strong interleukin (IL)-17 signature, and AD lesions had increased T helper (Th2) signaling. HS lesions had a more heterogeneous inflammatory profile involving TNF, IL-17, B cells, and NLR signaling. Weighted gene coexpression network analysis identified T-cell signaling and epidermal development as important characteristics of PsO lesions, while HS lesions were defined by complement activation, B-cell signaling, and fibroblast-associated pathways consistent with potential scarring in HS. Finally, gene expression analysis identified increased expression of B-cell-, plasma cell-, and immunoglobulin-associated genes in HS lesions relative to HC skin, PsO, and AD lesions. Discussion: These data suggest that HS pathogenesis is more heterogeneous than AD or PsO and highlight an important role of B and plasma cells in HS inflammation.