Immune-Based Cytokine Signatures of Prolonged Pandemic-Associated Chilblains

Area of Science:

• Immunology
• Dermatology
• Infectious Disease Epidemiology

Background:

• Pandemic-associated chilblains (PAC) typically resolve spontaneously.
• A subset of patients experiences persistent or recurrent PAC, necessitating further investigation into underlying mechanisms.

Purpose of the Study:

• To analyze peripheral cytokine profiles in patients with prolonged PAC.
• To elucidate the immunological characteristics differentiating prolonged PAC from acute cases.
• To identify potential therapeutic targets for chronic PAC.

Main Methods:

• Peripheral blood samples were collected from 17 patients with prolonged PAC.
• Cytokine profiles were analyzed using multiplex assays.
• Immune signatures were compared to those of acute PAC.

Main Results:

• Elevated levels of IFN-γ, CXCL10, CX3CL1, IL-16, CCL22, and S100A8 were identified in prolonged PAC.
• Prolonged PAC exhibits a type II interferon-skewed inflammatory signature, distinct from the type I interferon response in acute PAC.
• Evidence of T cell activation and endothelial involvement was observed.

Conclusions:

• Prolonged PAC is associated with a distinct type II interferon-driven inflammatory profile.
• Autoimmune comorbidities in some patients suggest pre-existing immune dysregulation contributes to chronicity.
• JAK inhibition and IFN-γ-directed therapies are potential treatment strategies for prolonged PAC.