R. John Looney
SCOTTSDALE, Ariz. — Although the role of type I interferon has been well-established for systemic lupus erythematosus, a type I interferon signature can be also seen in dermatomyositis, which emphasizes the importance of interferon in skin disease and opens new possibilities for therapeutic applications, according to a presentation here.
“It is interesting that some of the [recent data] show that JAK inhibitors may be particularly good for someone with skin rashes that we see in patients with autoimmune diseases associated with interferon,” R. John Looney, MD, professor of medicine at the Stephen I. Rosenfeld Professor of Allergy and Clinical Immunology at the University of Rochester, told attendees at the Seventh Annual Basic and Clinical Immunology for the Busy Clinician symposium.
He added, “While this has been demonstrated in lupus, it also seems to be true for dermatomyositis — there may be subsets of patients that do quite well with some of the JAK inhibitors that inhibit the interferon pathway.”
Citing the review from Selva-O’Callaghan and colleagues published in the Lancet Neurology, Looney noted that classification of patients with dermatomyositis vs. polymyositis was largely contingent on whether characteristic rashes accompanied the muscle involvement.
“The thing about dermatomyositis as opposed to polymyositis or myositis where you get necrosis without much inflammation is that you get this very vesicular atrophy,” Looney said. “The muscle cells in the center of the fascicle are fairly normal but as you get to the edge, that is where you find this atrophy. It is a very typical characteristic biopsy, and the pathologist can really make a call for dermatomyositis based on this.”
Additionally, Looney emphasized that the type I interferon pathway has demonstrated involvement of the pathogenesis of dermatomyositis and has been observed to be upregulated in the muscle and skin tissue, as well as peripheral blood cells. Given the upregulation of type I interferon pathway observed in dermatomyositis, JAK inhibition could provide a new avenue for treatment.
“Interferonopathies are a fascinating aspect of monogenic autoinflammatory diseases,” Looney said. “Originally, when it was just periodic fevers, we had this idea that we had these autoinflammatory diseases that didn’t involve the adaptive immune system; however, when you get into interferonopathies, you find that, in many cases, you actually do get activation of the adaptive immune system and they can begin to look like lupus and some of our other diseases.” – by Robert Stott
Looney LH. Translational advances in miscellaneous IMIDs. Presented at: Seventh Annual Basic and Clinical Immunology for the Busy Clinician; February 15-16, 2019; Scottsdale, Ariz.
Disclosure: Looney reports he is a consultant for Genentech and Roche Laboratories.