Work

Janus kinase/signal transducer and activator of transcription signalling pathway is involved in the immune mechanism of bullous pemphigoid

Year: 2025

Type: article

Abstract: 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.

Source: British Journal of Dermatology

DOI: 10.1093/bjd/ljaf219