Dysregulated CD38 expression in blood and skin immune cells of patients with hidradenitis suppurativa.

Background: Hidradenitis suppurativa (HS) is a multifactorial, inflammatory skin disease. Increased systemic inflammatory comorbidities and serum cytokines highlight systemic inflammation as a feature of HS. However, the specific immune cell subsets contributing to systemic and cutaneous inflammation have not been resolved.

Objective: Identify features of peripheral and cutaneous immune dysregulation.

Methods: Here, we generated whole-blood immunomes by mass cytometry. We performed a meta-analysis of RNA-seq data, immunohistochemistry, and imaging mass cytometry to characterize the immunological landscape of skin lesions and perilesions from patients with HS.

Results: Blood from patients with HS exhibited lower frequencies of natural killer cells, dendritic cells, and classical (CD14+CD16-) and nonclassical (CD14-CD16+) monocytes, as well as higher frequencies of Th17 cells and intermediate (CD14+CD16+) monocytes than blood from healthy controls. Classical and intermediate monocytes from patients with HS had increased expression of skin-homing chemokine receptors. Furthermore, we identified a CD38+ intermediate monocyte subpopulation that was more abundant in the immunome of blood from patients with HS. Meta-analysis of RNA-seq data found higher CD38 expression in lesional HS skin than in perilesional skin, and markers of classical monocyte infiltration. Imaging mass cytometry showed that CD38+ classical monocytes and CD38+ monocyte-derived macrophages were more abundant in lesional HS skin.

Conclusion: Overall, we report targeting CD38 may be worth pursuing in clinical trials.

Key Messages: 3.Monocyte subsets express markers of activation in circulation and HS lesionsTargeting CD38 may be a viable strategy for treating systemic and cutaneous inflammation in patients with HS.

Capsule Summary: 4.Dysregulated immune cells in patients with HS express CD38 and may be targeting by anti-CD38 immunotherapy.