Using the circulating proteome to assess type I interferon activity in systemic lupus erythematosus

Area of Science:

• Immunology
• Biochemistry
• Genetics

Background:

• Type I interferon (IFN) plays a key role in systemic lupus erythematosus (SLE) pathology.
• Current methods to track IFN activity rely on measuring IFN-inducible gene transcripts in blood.

Purpose of the Study:

• To investigate if circulating proteins can serve as biomarkers for global IFN activity in SLE.
• To develop and validate a novel protein signature for IFN activity in SLE patients.

Main Methods:

• Generated 1,132 aptamer-based protein measurements from SLE patient blood samples.
• Derived an IFN protein signature (IFNPS) and compared it to the IFN 21-gene signature (IFNGS).
• Analyzed correlation of IFNPS with immune cell activation, disease activity, and response to anifrolumab treatment.

Main Results:

• The developed IFNPS approximated the IFNGS, identifying elevated IFN activity in 89% of IFNGS-high SLE patients.
• IFNPS identified a subset of patients with IFN activity but without elevated IFNGS.
• IFNPS correlated with global SLE disease activity and decreased after type I IFN neutralization with anifrolumab.

Conclusions:

• A novel protein signature (IFNPS) effectively reflects type I IFN activity in SLE patients.
• IFNPS can identify a distinct subset of SLE patients with IFN activity.
• IFNPS serves as a valuable tool for monitoring disease activity and treatment response in SLE.