OBJECTIVE: To identify disease-related genes and immune-regulatory pathways in 
the pathogenesis of systemic lupus erythematosus (SLE) by using gene expression 
profiling and protein-protein interaction analysis.
METHODS: Peripheral white blood cell gene expression profiles of 10 SLE patients 
were determined by oligonucleotide microarray analysis. Clustering of the gene 
expression profile was compared with the clinical immune phenotype. SLE-induced 
genes that were over- or under-expressed were determined and independently 
validated using a real-time polymerase chain reaction (PCR) method. To study 
their potential function and the possible pathways involved, a candidate gene 
was cloned and a GST (glutathione S-transferase) fusion protein was expressed in 
Escherichia coli. The fusion protein was further purified using the glutathione 
Sepharose 4B system, and was treated as bait to capture prey from SLE peripheral 
white blood cell lysate. MALDI-TOF (matrix-assisted laser 
desorption/ionization-time-of-flight) mass spectrometry was then performed to 
determine the prey protein.
RESULTS: Similarity was found between the gene expression profile and the immune 
phenotype clusters of the SLE patients. More than 20 disease-associated genes 
were identified, some of which have not been related to SLE previously. Of these 
genes, a cluster of interferon-induced genes were highly correlated. IFIT1 
(interferon-induced with tetratricopeptide repeats 1) was one of these genes, 
and overexpression of its mRNA was confirmed independently by real-time PCR in a 
larger population (40 SLE patients and 29 normal controls). An IFIT1 protein- 
protein interaction study showed that IFIT1 may interact with Rho/Rac guanine 
nucleotide exchange factor.
CONCLUSION: The gene expression profile seems to be the molecular basis of the 
diverse immune phenotype of SLE. On the basis of the SLE-related genes found in 
this study, we suggest that the interferon-related immune pathway is important 
in the pathogenesis of SLE. IFIT1 is the first gene described as a candidate 
gene for SLE, and may function by activating Rho proteins through interaction 
with Rho/Rac guanine nucleotide exchange factor. IFIT1 and the 
interferon-related pathway may provide potential targets for novel interventions 
in the treatment of SLE.