OBJECTIVE: To characterize baseline gene expression and pharmacodynamically 
induced changes in whole blood gene expression in 1,760 systemic lupus 
erythematosus (SLE) patients from 2 phase III, 52-week, randomized, 
placebo-controlled, double-blind studies in which patients were treated with the 
BAFF-blocking IgG4 monoclonal antibody tabalumab.
METHODS: Patient samples were obtained from SLE patients from the ILLUMINATE-1 
and ILLUMINATE-2 studies, and control samples were obtained from healthy donors. 
Blood was collected in Tempus tubes at baseline, week 16, and week 52. RNA was 
analyzed using Affymetrix Human Transcriptome Array 2.0 and NanoString.
RESULTS: At baseline, expression of the interferon (IFN) response gene was 
elevated in patients compared with controls, with 75% of patients being positive 
for this IFN response gene signature. There was, however, substantial 
heterogeneity of IFN response gene expression and complex relationships among 
gene networks. The IFN response gene signature was a predictor of time to 
disease flare, independent of anti-double-stranded DNA (anti-dsDNA) antibody and 
C3 and C4 levels, and overall disease activity. Pharmacodynamically induced 
changes in gene expression following tabalumab treatment were extensive, 
occurring predominantly in B cell-related and immunoglobulin genes, and were 
consistent with other pharmacodynamic changes including anti-dsDNA antibody, C3, 
and immunoglobulin levels.
CONCLUSION: SLE patients demonstrated increased expression of an IFN response 
gene signature (75% of patients had an elevated IFN response gene signature) at 
baseline in ILLUMINATE-1 and ILLUMINATE-2. Substantial heterogeneity of gene 
expression was detected among individual patients and in gene networks. The IFN 
response gene signature was an independent risk factor for future disease 
flares. Pharmacodynamic changes in gene expression were consistent with the 
mechanism of BAFF blockade by tabalumab.