Deciphering Immune Endotypes Within Drug Reaction With Eosinophilia and Systemic Symptoms (DRESS) Syndrome

Area of Science:

• Immunology
• Pharmacology
• Clinical Medicine

Background:

• Drug Reaction with Eosinophilia and Systemic Symptoms (DRESS) is a severe, delayed drug hypersensitivity.
• DRESS presentations range from mild to life-threatening, with unclear underlying immune mechanisms.
• Distinct clinical phenotypes may correlate with different immune signatures and pathomechanisms.

Purpose of the Study:

• To investigate systemic immune profiles in patients with DRESS syndrome.
• To determine if varying DRESS severity correlates with distinct inflammatory profiles.
• To explore potential immune signatures associated with different DRESS phenotypes.

Main Methods:

• Multicenter study including 26 DRESS patients and 6 healthy controls (HC).
• Serum samples collected at diagnosis.
• Targeted high-throughput proteomics assay (OLINK) measured 180 inflammation/immune response-associated proteins.

Main Results:

• DRESS patients exhibited systemic immune activation, with increased Type 2/eosinophil-axis cytokines (IL4, IL5, IL13) compared to HC.
• Upregulation of proinflammatory mediators (IL6, IL10, IFN-gamma) and immune regulators observed.
• Unsupervised clustering revealed three immune profiles: Group 1 (IL7, milder activation, older patients, longer hospitalization), Group 2 (Type 3 response, Th17 cytokines, TLR signaling, higher HIV prevalence), and Group 3 (high eosinophils, eosinophil mediators, Type 2 response).
• Significant overlap in inflammation-related proteins across severity grades, including chemokines and immune checkpoint molecules.

Conclusions:

• Targeted serum proteomics indicate systemic immune activation in DRESS, particularly involving the Type 2/eosinophil axis.
• Identification of distinct DRESS immune profiles suggests potential for patient stratification.
• Further validation could lead to more targeted DRESS treatment approaches.