Type III Interferons in Systemic Lupus Erythematosus Association Between Interferon λ3, Disease Activity, and Anti-Ro/SSA Antibodies

Objective: The aim of this study was to assess associations between serum type III (lambda) interferons (IFN-lambda) and disease activity in systemic lupus erythematosus (SLE). Methods: Serum levels of IFN-lambda 1, IFN-lambda 2, and IFN-lambda 3 were measured in 93 SLE patients and 67 healthy individuals. The associations with overall disease activity, organ-specific damage, and SLE-related antibodies were assessed. Results: Median IFN-lambda 1 levels were 0 pg/mL (range, 0-510 pg/mL) and 0 pg/mL (0-171 pg/mL; P = 0.814) in SLE patients and control subjects, respectively. These figures were 0 pg/mL (0-28 pg/mL) and 0 pg/mL (0-43 pg/mL; P = 0.659) for IFN-lambda 2, as well as 83 pg/mL (0-965 pg/mL) and 42 pg/mL (0-520 pg/mL; P = 0.002) for IFN-lambda 3, respectively. According to the Systemic Lupus Erythematosus Disease Activity Index categories, IFN-lambda 3 levels were 44 pg/mL (0-158 pg/mL) in quiescent, 117 pg/mL (0-344 pg/mL) in mild, 79 pg/mL (0-965 pg/mL) in moderate, and 78 pg/mL (0-329 pg/mL) in severe disease, with the highest levels found in patients with serosal or cutaneous involvement. In line with this, IFN-lambda 3 levels were inversely correlated with C3 (lambda = -0.44; 95% confidence interval, -0.62 to -0.20; P = 0.0003) and C4 (lambda = -0.40; 95% confidence interval, -0.59 to -0.15; P = 0.0001) complement proteins. In addition, higher IFN-lambda 3 levels were found in patients positive for anti-Ro/SSA antibodies than in those negative for that antibody (122 pg/mL [0-965 pg/mL] vs. 0 pg/mL [0-165 pg/mL]; P = 0.001). The concentration of IFN-lambda 3 also was higher in patients receiving glucocorticoids (104 pg/mL [0-965 pg/mL] vs. 30 pg/mL [0-165 pg/mL]; P = 0.009), and a dose-related effect was observed. Conclusions: Interferon lambda 3, a subtype of type III IFNs, is associated with the extent of lupus activity, in particular with active serosal and cutaneous disease. This association could be mechanistically related to anti-Ro/SSA antibodies.