Elevation of interferon type I (IFN-I) is associated with more severe disease in patients with systemic lupus erythematosus (SLE), although the relationship between elevated levels of IFN-I and SLE disease activity over time has not been defined. In particular, lupus nephritis is the most common severe manifestation of SLE and confers an increased risk for end-stage renal disease and death in patients with SLE. In a new retrospective study, Kirou and colleagues (ACR 2013; Abstract 1572) analyzed plasma samples from 57 patients with SLE for IFN-I levels, as well as clinical and other laboratory data, longitudinally over an average of 9 visits per patient. The IFN-I levels were analyzed based on the response of the WISH cell line to SLE patient plasma, which is sensitive to IFN-I stimulation and has a minimum detection level of 6 IU/mL when assayed using quantitative PCR. Normal plasma and a recombinant IFN-I standard were used as negative and positive controls, respectively. The patients were divided into 2 groups based on high or low IFN-I levels at baseline (study initiation).
Patients with SLE and high IFN-I plasma activity at baseline showed a 3.2-fold increased IFN-I plasma activity during follow-up visits compared with patients with low IFN-I plasma activity at baseline (P <.01). Compared with patients with low IFN-I plasma activity at baseline, the patients with high IFN-I plasma activity had significant decreases in peripheral blood C3 levels (P <.03), white blood cell counts (P <.04), absolute lymphocyte counts (P <.01), and a higher erythrocyte sedimentation rate (P <.02) and anti–ds-DNA titers (P <.02). Patients with high plasma IFN-I activity at the first study visit exhibited 1.4-fold greater disease activity during the study as measured by the SLE Disease Activity Index (SLEDAI; P <.02) or the British Isles Lupus Assessment Group (BILAG; P <.05).
Strikingly, patients with SLE and high IFN-I activity at study initiation demonstrated a 2.5-fold increase in renal BILAG activity (which can translate to a greater likelihood of developing lupus nephritis and end-stage renal disease), a 1.8-fold increase in neurologic BILAG activity, and worsened hematologic BILAG scores.
The authors concluded that measurement of IFN-I activity in plasma of patients with SLE may help identify patients at high risk for lupus nephritis and thus serve as an important disease monitoring biomarker. Furthermore, IFN-I appears to predict increased disease activity in neurologic and hematologic systems as detected by BILAG scores. However, for these conclusions to be useful, the measurement of plasma IFN-I must be made readily available and affordable for routine clinical practice.