Type I interferon (IFN) is implicated in systemic lupus erythematosus (SLE) pathogenesis. We aimed to identify type I IFN signaling-dependent and -independent molecular pathways in a large population of patients with SLE.
Baseline blood samples from adult patients with moderate to severe SLE from two Phase IIb studies (NCT01438489, 
Whole blood samples from IFNGS test-high patients were enriched versus IFNGS test-low patients for CD40L signaling (
Clinicaltrials.gov: NCT01438489 and NCT01283139.
IFNGS test-high patients overexpressed many gene signatures associated with SLE pathogenesis compared with IFNGS test-low patients, reflecting broad immune activation. These results provide new insights into the molecular heterogeneity underlying SLE pathogenesis, highlighting shared mechanisms beyond type I IFN, across several autoimmune diseases.