A clinically actionable stratification of bullous pemphigoid using a disease activity score reveals a targetable inflammatory endotype
British Journal of Dermatology, 2026
Cao Z., Kong S., Ye J., Hu W., Zhu Y., Tao Y., Che D., Yuan B., Gui Y., Raap U., Geng S., Peng B.
| Disease area | Application area | Sample type | Products |
|---|---|---|---|
Immunological & Inflammatory Diseases Dermatological Diseases | Patient Stratification | Serum |  Olink Target 96 |
Abstract
Background
Bullous pemphigoid (BP) exhibits significant clinical heterogeneity. The molecular drivers underlying these distinct phenotypes remain poorly understood, hindering the development of precision medicine approaches.
Objectives
To correlate clinical phenotypes, defined by the Bullous Pemphigoid Disease Area Index (BPDAI), with molecular endotypes using serum proteomic profiling.
Methods
This cohort study enrolled 143 hospitalized patients with BP at a tertiary centre between January 2024 and June 2025. Patients were stratified into inflammatory BP (I-BP; BPDAI urticaria/erythema subscore ≥5) and pauci-inflammatory BP (PI-BP; subscore <5) based on the first quartile of the subscore. Clinical features, laboratory parameters, and treatment outcomes were compared. Serum proteomic profiling (Olink Target 96 Inflammation) was performed in a representative subset (n=37).
Results
Among 143 patients (mean age 73.9 years; 58.7% male), 108 (75.5%) were classified as I-BP and 35 (24.5%) as PI-BP. Compared to PI-BP, I-BP patients were younger, had more severe pruritus, and exhibited significantly elevated peripheral eosinophil counts (0.6 vs 0.2 ×109/L; P=0.001) and serum IL-5 levels (52.5 vs 3.9 pg/mL; P=0.007). Despite receiving more intensive therapy, I-BP patients required a longer median hospital stay (8 vs 7 days; P=0.029). Proteomic analysis identified eight differentially expressed proteins. IL-13, thymic stromal lymphopoietin (TSLP), oncostatin M (OSM), and MCP-4 were upregulated in I-BP and showed positive correlation with the urticaria/erythema subscore (P<0.05) but not with the erosions/blisters subscore. IL-13 demonstrated the highest diagnostic accuracy for the I-BP endotype (AUC=0.87). Functional enrichment analysis confirmed differential activation of type 2 inflammation and the JAK-STAT signaling pathway in the I-BP group.
Conclusions
The BPDAI urticaria/erythema subscore serves as a reliable clinical surrogate for a Th2-driven molecular endotype in BP. The identification of a specific Th2-ligand/JAK-STAT-signaling circuit in the inflammatory phenotype supports a stratified treatment approach, suggesting that patients with a high inflammatory burden may benefit from targeted type 2 immunotherapies or JAK inhibitors, which warrants further prospective validation.