New insights into rare autoimmune disorder

Dermatomyositis is a rare and devastating autoimmune disease primarily affecting the skin and skeletal muscle.

While both can affect the muscle, dermatomyositis and lupus show many overlapping clinical and pathological features in their associated skin rashes but a differing response to available therapeutics.

Better understanding of the immunopathology in dermatomyositis, the cellular characteristics and the modular differences in lesional and non-lesional skin in dermatomyositis and lupus patients can give insight for more effective treatments.

At University of Michigan Health, a team of researchers led by Michelle Kahlenberg, M.D., Ph.D., Vice Chair of Research for the Department of Internal Medicine and Michael H. and Maricia S. Klein Professor of Rheumatic Disease at U-M Health observed distinct differences in the skin of dermatomyositis patients using single-cell RNA sequencing.

Dr. Kahlenberg is co-leader of a Taubman Institute Innovation Project team, and Taubman Institute support contributed to this research. 

The study published in Science Translational Medicine, analyzed lesional and non-lesional lupus and dermatomyositis skin, healthy control skin and peripheral blood.

The findings revealed a unique, inflammatory monocyte population within the skin and blood of dermatomyositis patients.

These monocytes contributed to endothelial dysfunction and apoptosis.

“Our research demonstrated a pervasive type one interferon signature in dermatomyositis and lupus skin that likely explains some overlapping features such as photosensitivity,” said Kahlenberg.

“However, the endothelial cells in dermatomyositis rashes looked unhealthy, which is was not observed to the same extent in the lupus skin.”

Further testing their theory of monocyte-endothelial cell interplay in dermatomyositis skin, Kahlenberg and team introduced medical inhibition of the JAK1 protein to the data set.

Upon JAK1 inhibition, endothelial cell death and inflammatory signature were reversed in dermatomyositis endothelial cells, highlighting JAK1protein inhibition as a therapeutic avenue of treatment.

“Together, this data provides a comprehensive cross-disease characterization of lesional and non-lesional skin in dermatomyositis and gives evidence on why JAK1 inhibition may offer therapeutic hope for dermatomyositis patients,” said Kahlenberg.

The next steps for Kahlenberg’s team will include further mechanistic testing of JAK1 inhibition as a treatment method for dermatomyositis with the intention of opening a better treatment pathway for dermatomyositis patients.