Danby Research Grant Supports New Insights into HS

Today

With support from the HS Foundation’s Danby Research Grant, Dr. Victoria Fang pursued research focused on understanding hidradenitis suppurativa (HS) at the cellular level. In this interview, she discusses how this funding allowed her team to explore the presence of tertiary lymphoid structures and germinal centers forming in HS tissue, and how these early insights may contribute to identifying treatment targets for patients with more severe disease.

Q: Tell me your HS Foundation research? 

A: Dr. Fang: The foundation grant REALLY launched my ability to do research in HS. The research I proposed was to understand at the cellular level what is happening in HS lesions. A lot of us know that you can send tissue for a few markers at a time to see what a cell in HS doing. As I was starting my post doc, we were able to look at a lot more markers all at the same time which allows us to figure out how cells interact and what factors are at play. We and others noted something called tertiary lymphoid structures. These are found in the liver, spleen, and other immune tissues, but they really shouldn’t be in the skin, and they are in the skin in HS.  Part of our hypothesis was trying to figure out if we could understand these structures better and determine if they play a role in HS. The ultimate goal was to determine if these tertiary lymphoid structures (TLSs) could be targets for treatments in the future.

Q: What do you anticipate are the next steps based on your work? 

A:  It turns out others have also found TLSes in HS -- Katherine Lu and I connected at SHSA a few years ago to discuss TLSes further and ultimately the two of us were able to collaborate, and recently she published work looking at these TLSes in more detail. We are reasonably certain now that beyond TLSes, we are seeing true germinal centers (almost like lymph nodes but lymph nodes developing on their own in the skin) that are building in the HS tissue. We are noticing B cell and plasma cells that often go along with germinal centers. We believe in a patient with severe HS with at least 4% BSA, that that patient may have more plasma cells in their skin than in all of their bone marrow. We are trying to identify the B-cells, T-cells, and plasma cell subsets that are upregulated in patients with more severe disease. As is the challenge with all translational work, it is hard to get to causation. The best we can say right now is that plasma cell numbers are very correlated with severe disease. We are now hypothesizing that at least 1 arm of the pathogenesis of HS, is that one aspect of the disease is triggering these TLSes.  

Q: Are there potential treatments for HS that derive from your research?

A: Ideally, we would have medications that target these axes and target the plasma cells. BTK inhibitors and other BAFF cell inhibitors have been evaluated for HS. CAR-Ts cells which are modified T cells could also be an interesting treatment for HS if they were programmed towards an appropriate target.

Q: What does your career look like now?

A: Recently, I had the opportunity to join industry to partner in getting to do science and bring medications to patients more quickly. I am also collaborating with HS colleagues at The University of Pennsylvania and seeing patients at the University of Pennsylvania with HS as well.