OBJECTIVE: The interferon (IFN) signature is related to disease activity and 
vascular disease in systemic lupus erythematosus (SLE) and antiphospholipid 
syndrome (APS) and represents a promising therapeutic target. Quantification of 
the IFN signature is currently performed by gene expression analysis, limiting 
its current applicability in clinical practice. Therefore, the objective of this 
study was to establish an easy to measure biomarker for the IFN signature.
METHODS: Serum levels of galectin-9, CXCL-10 (IP-10) and tumour necrosis factor 
receptor type II (TNF-RII) were measured in patients with SLE, SLE+APS and 
primary APS (PAPS) and healthy controls (n=148) after an initial screening of 
serum analytes in a smaller cohort (n=43). Analytes were correlated to measures 
of disease activity and the IFN signature. The performance of galectin-9, 
CXCL-10 and TNF-RII as biomarkers to detect the IFN signature was assessed by 
receiver operating characteristic curves.
RESULTS: Galectin-9, CXCL-10 and TNF-RII were elevated in patients with SLE, 
SLE+APS and PAPS (p<0.05) and correlated with disease activity and tissue factor 
expression. Galectin-9 correlated stronger than CXCL-10 or TNF-RII with the IFN 
score (r=0.70, p<0.001) and was superior to CXCL-10 or TNF-RII in detecting the 
IFN signature (area under the curve (AUC) 0.86). Importantly, in patients with 
SLE(±APS), galectin-9 was also superior to anti-dsDNA antibody (AUC 0.70), or 
complement C3 (AUC 0.70) and C4 (AUC 0.78) levels in detecting the IFN 
signature.
CONCLUSION: Galectin-9 is a novel, easy to measure hence clinically applicable 
biomarker to detect the IFN signature in patients with systemic autoimmune 
diseases such as SLE and APS.