2'5'-Oligoadenylate synthetase (OAS) was shown to be related to systemic lupus erythematosus (SLE) 20 years ago, and was rediscovered to be involved in type I interferon pathway in SLE by several microarray gene expression studies recently. The goal of this study was to investigate OAS isoform expressions in lupus patients, to evaluate whether they could become biomarkers to differentiate between disease flare and infection. Fifty-four SLE patients presented with fever or systemic inflammatory syndrome, or both, were enrolled. Gene expressions of OAS1, OAS2, and OASL were studied by using real time PCR in active SLE (SLEDAI >or=9, n=29) and in those complicated with infections (n=25). The latter group was composed of 19 patients with invasive bacterial infections, and six patients with viral infections. C reactive protein (CRP) and other clinical parameters were also measured. Twenty-nine healthy individuals made up a normal control group. The mRNA expressions of OAS1, OAS2, and OASL were higher in patients with lupus flares than those with infections (p<0.03), or normal controls (p<0.001). SLE complicated with infections have higher OAS1 expression level (P=0.002), lower OASL (P=0.004), and equivalent OAS2 (P=0.135), when compared with those of normal controls. OASL expression level was negatively correlated with infection in lupus by logistic regression analysis (p=0.008). Area under the receiver operating characteristic curve for the prediction of infection was 0.92 (p<0.0001) for OASL, and 0.77 (p=0.007) for CRP. Therefore, our preliminary data suggest that the pattern of OAS isoform expressions, OASL in particular, may provide useful information in differentiating disease flares from certain infections in SLE.