Autoantibody and cytokine profiles during treatment with belimumab in patients with systemic lupus erythematosus

Research output: Contribution to journalArticle

Abstract

We investigated whether belimumab treatment impacts on levels of autoantibodies and cytokines of interest in systemic lupus erythematosus (SLE). Longitudinally collected serum samples from 78 belimumab-treated Swedish SLE patients were analysed. Serum cytokine levels were determined using Luminex xMAP technology, and nuclear antigen autoantibody specificities using addressable laser bead immunoassay. In patients with detectable levels at baseline, interferon (IFN)-α2 levels were lower at month 6 (median; interquartile range (IQR): 8.9; 1.5–54.9 pg/mL) versus baseline (28.4; 20.9–100.3 pg/mL; p = 0.043). Interleukin (IL)-6 (baseline: 7.1; 2.9–16.1 pg/mL) decreased from month 6 (0.5; 0.5–6.3 pg/mL; p = 0.018) and throughout a 24 month follow-up. IL-10 (baseline: 12.6; 2.8–29.7 pg/mL) showed more rapid decreases from month 3 (1.8; 0.6–9.1 pg/mL; p = 0.003). Levels of anti-dsDNA (p < 0.001), anti-Smith antigen (Sm) (p = 0.002), anti-U1 small nuclear ribonucleoprotein (U1RNP) (p < 0.001), anti-Sm-U1RNP complex (p = 0.028), and anti-ribosomal P (p = 0.012) antibodies decreased from month 3 and remained decreased. Anti-Sm positivity at baseline was associated with higher probability and/or shorter time to achieve sustained SLE responder index-4 response (hazard ratio (HR): 2.52; 95% CI: 1.20–5.29; p = 0.015), independently of other factors. Decline of IL-6 levels through month 3 was greater in responders. In summary, belimumab treatment lowered IFN-α2, IL-6, and IL-10 levels, as well as levels of multiple autoantibodies, however after different time spans. Notably, anti-Sm positivity and early decline in IL-6 levels were associated with favorable treatment outcome.

Details

Authors
  • Ioannis Parodis
  • Emil Åkerström
  • Christopher Sjöwall
  • Azita Sohrabian
  • Andreas Jönsen
  • Alvaro Gomez
  • Martina Frodlund
  • Agneta Zickert
  • Anders A. Bengtsson
  • Johan Rönnelid
  • Iva Gunnarsson
Organisations
External organisations
  • Karolinska Institutet
  • Karolinska University Hospital
  • Linköping University
  • Uppsala University
  • Skåne University Hospital
Research areas and keywords

Subject classification (UKÄ) – MANDATORY

  • Rheumatology and Autoimmunity

Keywords

  • Autoantibodies, Autoimmunity, B cells, Biologic therapies, Cytokines, Immune complexes, Systemic lupus erythematosus
Original languageEnglish
Article number3463
JournalInternational Journal of Molecular Sciences
Volume21
Issue number10
Publication statusPublished - 2020 May 14
Publication categoryResearch
Peer-reviewedYes