Episode 14 - JAK/STAT signalling in bullous pemphigoid

In this episode of BJD Talks, Sam and Meera discuss the article ‘Janus kinase/signal transducer and activator of transcription signalling pathway is involved in the immune mechanism of bullous pemphigoid’ by H-Y Chung et al. The full article can be accessed at https://doi.org/10.1093/bjd/ljaf219 

*This podcast was generated by an AI tool created by 67Bricks for the British Association of Dermatologists* 

Transcript

SPEAKER_00 0:00

Welcome to BJD Talks, the official podcast of the BJD. I'm Sam.

SPEAKER_01 0:04

And I'm Mira. In this episode, we will be discussing the article by Xin Yu Chung et al, Janus kinase slash signal transducer and activator of transcription signalling pathway, is involved in the immune mechanism of bullus penthagoid from June 2025.

SPEAKER_00 0:21

Bullus penthagoid, or BP, is the most common autoimmune blistering skin condition, primarily affecting older adults. It's debilitating, chronic, and still lacks truly effective treatments. So, the study's findings on the potential for JAC inhibitors are especially thought-provoking.

SPEAKER_01 0:40

Yes, BP is a challenging disease caused by autoantibodies targeting hemidesmosomes at the dermoepidermal junction, culminating in inflammation and blisters. Conventional treatments like corticosteroids and immunosuppressants often bring unwanted side effects, especially for older patients. This study offers insights into the role of the Jackstat pathway in BP while also exploring newer treatment avenues. Let's touch on the methods first.

SPEAKER_00 1:08

The study included 50 patients with BP and 31 healthy donors as controls. Researchers examined skin tissue and plasma, focusing on the gene expression related to the JAKSTAT pathway and the cytokine profiles. They also tested JAC inhibitors, specifically TOFACitinib and Ritlacitinib, through an in vitro T cell activation assay to assess their effects on inflammatory proteins. Additionally, eight steroid-resistant BP patients received oral tofacetinib, and their clinical outcomes were tracked.

SPEAKER_01 1:40

The results were compelling. JAC3 and STAT-3 mRNA levels were significantly higher in BP lesions compared to healthy controls. Elevated levels of pro-inflammatory cytokines such as interleukin-5, CCL17, and Granzyme B were observed in both the skin and plasma of BP patients. It's quite fascinating how they pinpointed the JACSTAT pathway's role in the inflammatory mechanism.

SPEAKER_00 2:08

The performance of the JAC inhibitors was particularly noteworthy. Both tofacitinib, a JAC1-3 inhibitor, and Ritlacitinib, a JAC3-specific inhibitor, significantly reduced inflammatory markers like Granzyme B and CCL17 in lab experiments. Clinically, five of the eight steroid-resistant BP patients treated with Topacitinib showed a marked decrease in disease activity within five weeks.

SPEAKER_01 2:34

That's quite remarkable. Reducing the bullis pemphigoid disease area index from 104.2 to 34.8 in under two months stands out. For severe or steroid-resistant BP cases, JAK inhibitors could indeed prove transformative.

SPEAKER_00 2:49

Of course, there are caveats. The study was retrospective and involved a small cohort, making larger clinical trials necessary to validate these findings. Moreover, safety concerns arise with JAC inhibitors, particularly in elderly patients, given potential adverse effects like cytopenia and liver function issues.

SPEAKER_01 3:09

Absolutely. The authors themselves stressed the importance of further trials to better establish efficacy and safety. That being said, this research represents an exciting step towards more targeted therapies in dermatology, aligning with the broader trend of precision medicine.

SPEAKER_00 3:25

True. A particularly promising approach might involve combining JAC inhibitors with low-dose steroids to balance efficacy and minimize side effects. It could greatly enhance the management of steroid-resistant BP.

SPEAKER_01 3:38

To summarise, the study highlights the critical role of the JAC stat pathway in BP's pathogenesis. Tophacitinib and similar inhibitors show potential in lowering inflammatory biomarkers and improving outcomes for refractory cases. However, further research is essential to confirm these early findings and ensure long term safety.

SPEAKER_00 4:00

It's a promising development, and I'm eager to see where this research will lead. Thanks for joining us for this episode of BJD Talks. Stay curious, keep learning, and we'll see you next time.