The British journal of dermatology · 2025
Janus kinase/signal transducer and activator of transcription signalling pathway is involved in the immune mechanism of bullous pemphigoid.
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Chung Hsin-Yu, Chen Chun-Bing, Lee Hua-En, Lu Chun-Wei, Chen Wei-Ti, Hui Rosaline Chung-Yee, Chi Min-Hui, Chang Ya-Ching, Lo Pei-Chi, Wang Chuang-Wei, Chung Wen-Hung
Аннотация
BACKGROUND: Bullous pemphigoid (BP) is a common immunobullous disease that mainly affects older people; however, the molecular pathogenesis of the Janus kinase/signal transducer and activator of transcription (JAK/STAT) pathway in BP is not fully understood.
OBJECTIVES: To characterize the immune profiles of and the key JAK/STAT pathway in patients with BP. The clinical efficacy of JAK inhibition in patients with BP was also assessed.
METHODS: Skin transcriptome profiling, measurement of plasma cytokine/chemokine levels, and an in vitro T-cell activation and JAK inhibitor (JAKi) blocking assay were performed for patients with BP. The clinical improvement in steroid-resistant patients with BP treated with JAKi was evaluated.
RESULTS: Fifty patients with BP and 31 healthy donor individuals were enrolled in this study. JAK3 and STAT3 mRNA levels were increased in skin lesions from patients with BP. BP-related inflammatory-mediated cytokines/chemokines, including interleukin 5, CCL22, CCL17, CCL18, matrix metalloproteinase 9 and granzyme B, were significantly elevated in patients with BP compared with the healthy donors (all P < 0.001). An in vitro T-cell activation and JAKi blocking assay revealed that tofacitinib (JAK1/3i) and ritlecitinib (JAK3i) had better inhibitory effects than upadacitinib on granzyme B and CCL17 in patients with BP. Eight patients with steroid-resistant BP were treated with oral tofacitinib. Of these patients, five had a rapid reduction in their Bullous Pemphigoid Disease Area Index (from 104.2 to 34.8) within 5 weeks.
CONCLUSIONS: JAK3i can attenuate JAK3/STAT3-mediated inflammatory factors, providing an alternative treatment strategy for patients with refractory BP in combination with low-dose steroids.
OBJECTIVES: To characterize the immune profiles of and the key JAK/STAT pathway in patients with BP. The clinical efficacy of JAK inhibition in patients with BP was also assessed.
METHODS: Skin transcriptome profiling, measurement of plasma cytokine/chemokine levels, and an in vitro T-cell activation and JAK inhibitor (JAKi) blocking assay were performed for patients with BP. The clinical improvement in steroid-resistant patients with BP treated with JAKi was evaluated.
RESULTS: Fifty patients with BP and 31 healthy donor individuals were enrolled in this study. JAK3 and STAT3 mRNA levels were increased in skin lesions from patients with BP. BP-related inflammatory-mediated cytokines/chemokines, including interleukin 5, CCL22, CCL17, CCL18, matrix metalloproteinase 9 and granzyme B, were significantly elevated in patients with BP compared with the healthy donors (all P < 0.001). An in vitro T-cell activation and JAKi blocking assay revealed that tofacitinib (JAK1/3i) and ritlecitinib (JAK3i) had better inhibitory effects than upadacitinib on granzyme B and CCL17 in patients with BP. Eight patients with steroid-resistant BP were treated with oral tofacitinib. Of these patients, five had a rapid reduction in their Bullous Pemphigoid Disease Area Index (from 104.2 to 34.8) within 5 weeks.
CONCLUSIONS: JAK3i can attenuate JAK3/STAT3-mediated inflammatory factors, providing an alternative treatment strategy for patients with refractory BP in combination with low-dose steroids.