233 Defining subsets in sle: the interplay among ifn-λ1, ifn-α and th17 axis cytokines

Background and aims Interferon (IFN)-αs are pivotal in systemic lupus erythematosus (SLE), and type III IFNs (IFN-λs) were recently also associated with SLE. We investigated levels of IFN-α and IFN-λ1, and related cytokines in SLE patients and controls. Methods We included 261 SLE patients and 261 population controls. All were examined and assessed for current organ manifestations and disease activity/damage using SLAM, SLEDAI and ACR/SDI scales. Levels of IFN-λ1, IFN-α, IL-17A, IL-23 and IP-10 were measured by ELISA. Results IFN-λ1 and IFN-α were detected in 29% and 44% of patients respectively, but their levels did not correlate. High serum levels of IFN-λ1 were positively associated with anti-nucleosome antibodies and lymphopenia, but negatively with musculoskeletal damage. Positive correlations between levels of IFN-λ1, IL-17A and IL-23 were observed. Patients with high levels of these three cytokines had more disease damage, especially renal. High levels of IFN-α were associated with mucocutaneous disease, leukopenia, low complement, Ro/SSA and La/SSB, whereas vascular events and antiphospholipid antibodies (aPL) were uncommon. We identified two subgroups with high disease activity: one double IFN-λ1 and IFN-α high and another IP-10 high. The former had more neuropsychiatric manifestations, while the latter had more arthritis. Conclusions Measurements of circulating IFN-λ1 and IFN-α define SLE patients with different characteristics. Levels of IFN-λ1 correlate with Th17 cytokines and identify a subgroup with more damage. Disease activity is associated with either upregulation of both type I and III IFNs, or independently with IP-10. Our findings could be of major importance when tailoring therapy for SLE patients with agents targeting IFN-pathways.