Article Text

Download PDFPDF

PO.3.67 Measuring IFNA2 levels by a single-molecule array in clinical practice of childhood-onset sle patients does matter; results from a single center longitudinal study
  1. Marleen Verkaaik,
  2. Wahadat M Javad,
  3. Hongchao Qi,
  4. Cornelia G van Helden-Meeuwsen,
  5. Erika Huijser,
  6. Lotte van den Berg,
  7. Jens Göpfert,
  8. Marleen Verkaaik,
  9. Marco Schreurs,
  10. Sylvia Kamphuis and
  11. Marjan A Versnel
  1. Dept. Immunology, Erasmus University Medical Center, Rotterdam, The Netherlands, Dept. Paediatric Rheumatology, Sophia Children’s hospital, Erasmus University Medical Center, Rotterdam, The Netherlands, Department of Biostatistics, Erasmus University Medical Center, Rotterdam, The Netherlands, NMI Natural and Medical Sciences Institute at the University of Tübingen, Dep. of Applied, Biomarkers and Immunoassays, Reutlingen, Germany


Introduction Type-I interferon (IFN-I) pathway activation plays a pivotal role in the pathogenesis of SLE and has been proposed as biomarker for disease activity. IFN-I pathway activation can be measured by determining the expression of IFN-I stimulated genes or a so-called IFN signature. Ultrasensitive single-molecule array (Simoa) technology enables measurement of IFN protein concentrations at subfemtomolar concentrations. Parallel use of these measuring methods in longitudinal cohorts of childhood-onset SLE (cSLE) patients in relation to disease activity could help in translating the most relevant technique for use in clinical practice.

Objective To determine the association of serum IFNa2 levels and whole blood IFN-I stimulated gene expression with disease activity and study their potential to mark specific disease activity states in a longitudinal cohort of cSLE patients.

Methods Serum IFNa2 levels were measured in 338 samples from 48 cSLE patients and 67 healthy controls using an IFN-a2 Simoa assay (Quanterix) on an HD-X analyser. A 5 gene IFN-I signature was measured by RT-PCR in paired whole blood samples. Disease activity was assessed by the clinical SELENA-SLEDAI (cSLEDAI) and BILAG-2004. Low disease activity was defined by the Low Lupus Disease Activity State (LLDAS) and flares were characterized by the SELENA-SLEDAI flare index. Analysis was performed using linear mixed effect models.

Results A clear positive correlation was present between serum IFNa2 levels and the IFN-I gene signature (r=0.78, p<0.0001). Serum IFNa2 levels and the IFN-I gene signature showed the same significant negative trend in the first three years after diagnosis. In this timeframe, mean baseline serum IFNa2 levels decreased with 55.1% (delta 172 fg/mL, p<0.001) to a mean value of 164fg/mL, which was below the calculated threshold of 219.4 fg/mL. In the linear mixed model, serum IFNa2 levels were significantly associated with both the cSLEDAI and the BILAG-2004 (p<0.001 and p<0.01), while the IFN-I gene signature did not show this association (p=0.35 and p=0.23). Moreover, 69.7% of the time points in LLDAS had a serum IFNa2 level under the calculated threshold, while only 31.9% of the time points in LLDAS reached an IFN-I gene signature below the calculated threshold. Both techniques were equally capable of marking disease flares (79.2% above threshold vs 87.5% above threshold).

Conclusions Serum IFNa2 levels measured by Simoa, but not the type-I IFN gene signature, are associated with disease activity scores and characterize disease activity states in cSLE patients. Hence, this technique has the potential to be implemented in clinical practice.

This is an open access article distributed in accordance with the Creative Commons Attribution Non Commercial (CC BY-NC 4.0) license, which permits others to distribute, remix, adapt, build upon this work non-commercially, and license their derivative works on different terms, provided the original work is properly cited, appropriate credit is given, any changes made indicated, and the use is non-commercial. See:

Statistics from

Request Permissions

If you wish to reuse any or all of this article please use the link below which will take you to the Copyright Clearance Center’s RightsLink service. You will be able to get a quick price and instant permission to reuse the content in many different ways.