Sep 30, 2026 · 15 min · 9 segments
In this podcast, expert clinicians examine the role of type 1 interferon signaling in the pathogenesis of cutaneous lupus erythematosus (CLE) and emerging therapeutic strategies targeting this…
Victoria WerthHost
So, Maria, to start, we would like to set the stage in terms of what's our current understanding of the role of interference signaling as a disease driver in cutaneous lupus.
And I know that you've done so much work in this area and you'll be able to educate all of us.
But it's quite interesting, right, in that we've learned that type 1 interferon is a primary mediator of pathogenesis of cutaneous lupus.
out quite nicely we know that a variety of cell types that infiltrate the skin as well as keratinocytes themselves produce type 1 interferon and that type 1 interferon is critical in the pathogenesis of photosensitivity and the full plethora of cutaneous manifestations that we see in cutaneous lupus.
And of course, the adaptive immune system also plays a role, but we think that paramount type 1 interferon is critical.
I mean, I think we know that patients with lupus have higher type 1 interferons in the keratinocytes that can go up even higher in response to ultraviolet radiation, which is a trigger.
And we know that interferons can upregulate various proteins in the skin and the epidermal junction, various cytokines and chemokines that bring in inflammatory cells.
that can then mediate further interferon production and then also sort of a feedback loop that just continues the process that we see in cutaneous lupus.
And thus, you know, the notion here is that a therapy such as anaphylumab, which specifically targets this pathway at the level of the receptor, would also be effective in lesions of CLE.
And in fact, anaphylumab has been a game changer in the treatment of cutaneous lupus in the setting of SLE, for which it is approved.
And what's been so striking about this therapy, in my experience, and what the literature has shown us, right, Vicki, is that this mechanism acts quickly and we see resolution of inflammation in the skin faster than we've seen with our other targeted therapies.
And I think this is really a proof of concept of the critical role importance of type 1 interferon in the pathogenesis of skin lesions, the fact that we can block the type 1 interferon receptor and see such a dramatic response has been quite striking and has been very helpful for our patients living with SLE with cutaneous manifestations.
And there is an ongoing phase three trial that is looking at patients with cutaneous lupus so that the drug would be accessible to more than just SLE patients.
So, Maria, to start, we would like to set the stage in terms of what's our current understanding of the role of interference signaling as a disease driver in cutaneous lupus.
And I know that you've done so much work in this area and you'll be able to educate all of us.
But it's quite interesting, right, in that we've learned that type 1 interferon is a primary mediator of pathogenesis of cutaneous lupus.
out quite nicely we know that a variety of cell types that infiltrate the skin as well as keratinocytes themselves produce type 1 interferon and that type 1 interferon is critical in the pathogenesis of photosensitivity and the full plethora of cutaneous manifestations that we see in cutaneous lupus.
And of course, the adaptive immune system also plays a role, but we think that paramount type 1 interferon is critical.
I mean, I think we know that patients with lupus have higher type 1 interferons in the keratinocytes that can go up even higher in response to ultraviolet radiation, which is a trigger.
And we know that interferons can upregulate various proteins in the skin and the epidermal junction, various cytokines and chemokines that bring in inflammatory cells.
that can then mediate further interferon production and then also sort of a feedback loop that just continues the process that we see in cutaneous lupus.
And thus, you know, the notion here is that a therapy such as anaphylumab, which specifically targets this pathway at the level of the receptor, would also be effective in lesions of CLE.
And in fact, anaphylumab has been a game changer in the treatment of cutaneous lupus in the setting of SLE, for which it is approved.
And what's been so striking about this therapy, in my experience, and what the literature has shown us, right, Vicki, is that this mechanism acts quickly and we see resolution of inflammation in the skin faster than we've seen with our other targeted therapies.
And I think this is really a proof of concept of the critical role importance of type 1 interferon in the pathogenesis of skin lesions, the fact that we can block the type 1 interferon receptor and see such a dramatic response has been quite striking and has been very helpful for our patients living with SLE with cutaneous manifestations.
And there is an ongoing phase three trial that is looking at patients with cutaneous lupus so that the drug would be accessible to more than just SLE patients.
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