Serum IFNα2 levels are associated with disease activity and outperform IFN-I gene signature in a longitudinal childhood-onset SLE cohort

Objective To study the association of serum IFN alpha 2 levels measured by ultrasensitive single-molecule array (Simoa) and the IFN-I gene signature (IGS) with disease activity and determine whether these assays can mark disease activity states in a longitudinal cohort of childhood-onset SLE (cSLE) patients. Methods Serum IFN alpha 2 levels were measured in 338 samples from 48 cSLE patients and 67 healthy controls using an IFN alpha Simoa assay. Five-gene IGS was measured by RT-PCR in paired whole blood samples. Disease activity was measured by clinical SELENA-SLEDAI and BILAG-2004. Low disease activity was defined by Low Lupus Disease Activity State (LLDAS) and flares were characterized by SELENA-SLEDAI flare index. Analysis was performed using linear mixed models. Results A clear positive correlation was present between serum IFN alpha 2 levels and the IGS (r = 0.78, P < 0.0001). Serum IFN alpha 2 levels and IGS showed the same significant negative trend in the first 3 years after diagnosis. In this timeframe, mean baseline serum IFN alpha 2 levels decreased by 55.1% (Delta 201 fg/ml, P < 0.001) to a mean value of 164 fg/ml, which was below the calculated threshold of 219.4 fg/ml that discriminated between patients and healthy controls. In the linear mixed model, serum IFN alpha 2 levels were significantly associated with both cSELENA-SLEDAI and BILAG-2004, while the IGS did not show this association. Both IFN-I assays were able to characterize LLDAS and disease flare in receiver operating characteristic analysis. Conclusions Serum IFN alpha 2 levels measured by Simoa technology are associated with disease activity scores and characterize disease activity states in cSLE.