Spatial transcriptomics maps early B-cell and T-cell activation in hidradenitis suppurativa.

Area of Science:

• Dermatology
• Immunology
• Molecular Biology

Background:

• Hidradenitis suppurativa (HS) is a chronic inflammatory skin condition with progressive dermal changes.
• The temporal relationship between immune activation and structural lesion formation in HS is not fully understood.

Purpose of the Study:

• To determine the sequence of immune activation relative to structural changes in early and late-stage hidradenitis suppurativa.
• To compare immune profiles of HS with acne conglobata and psoriasis.

Main Methods:

• Integrated spatial and single-cell transcriptomic analyses of early- and late-stage HS lesions.
• Comparison with acne conglobata and psoriasis samples.
• Analysis of 156 regions of interest using spatial transcriptomics.

Main Results:

• Early-stage HS exhibits significant dermal immune activation, including B-cell enrichment and type 17 T-cell (T17) pathway activation, preceding tunnel and tertiary lymphoid structure (TLS) formation.
• Single-cell RNA sequencing revealed early plasma cell expansion and multifunctional B-cells.
• T-cells, not fibroblasts, were the primary source of CXCL13 in early HS lesions.

Conclusions:

• Immune activation in HS is an early event that precedes structural remodeling, indicating an aggressive disease nature from onset.
• Targeting the T17 axis and B-cell inflammation early in HS may prevent disease progression.