Serum profiling identifies CCL8, CXCL13, and IL-1RA as markers of active disease in patients with systemic lupus erythematosus

Front Immunol. 2023 Nov 30:14:1257085. doi: 10.3389/fimmu.2023.1257085. eCollection 2023.

Abstract

Introduction: Systemic lupus erythematosus (SLE) is a clinically heterogeneous disease that presents a challenge for clinicians. To identify potential biomarkers for diagnosis and disease activity in SLE, we investigated a selected yet broad panel of cytokines and autoantibodies in patients with SLE, healthy controls (HC), and patients with other autoimmune diseases (AIDs).

Methods: Serum samples from 422 SLE patients, 546 HC, and 1223 other AIDs were analysed within the frame of the European PRECISESADS project (NTC02890121). Cytokine levels were determined using Luminex panels, and autoantibodies using different immunoassays.

Results: Of the 83 cytokines analysed, 29 differed significantly between patients with SLE and HC. Specifically, CCL8, CXCL13, and IL-1RA levels were elevated in patients with active, but not inactive, SLE versus HC, as well as in patients with SLE versus other AIDs. The levels of these cytokines also correlated with SLE Disease Activity Index 2000 (SLEDAI-2K) scores, among five other cytokines. Overall, the occurrence of autoantibodies was similar across SLEDAI-2K organ domains, and the correlations between autoantibodies and activity in different organ domains were weak.

Discussion: Our findings suggest that, upon validation, CCL8, CXCL13, and IL-1RA could serve as promising serum biomarkers of activity in SLE.

Keywords: antiphospholipid syndrome; autoantibodies; autoimmunity; biomarkers; cytokines; diagnosis; systemic lupus erythematosus.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Autoantibodies
  • Autoimmune Diseases*
  • Biomarkers
  • Chemokine CCL8
  • Chemokine CXCL13
  • Cytokines
  • Humans
  • Interleukin 1 Receptor Antagonist Protein
  • Lupus Erythematosus, Systemic*

Substances

  • Interleukin 1 Receptor Antagonist Protein
  • Cytokines
  • Biomarkers
  • Autoantibodies
  • CCL8 protein, human
  • Chemokine CCL8
  • CXCL13 protein, human
  • Chemokine CXCL13

Grants and funding

The author(s) declare financial support was received for the research, authorship, and/or publication of this article. IP has received grants from the Swedish Rheumatism Association (R-969696), King Gustaf V’s 80-year Foundation (FAI-2020-0741), Swedish Society of Medicine (SLS-974449), Nyckelfonden (OLL-974804), Professor Nanna Svartz Foundation (2021-00436), Ulla and Roland Gustafsson Foundation (2021-26), Region Stockholm (FoUI-955483), and Karolinska Institutet. This work has received funding from the Innovative Medicines Initiative (IMI) Joint Undertaking (JU) for the PRECISESADS project (grant number 115565), as well as from the IMI 2 JU for the 3TR project (grant number 831434). The JU receives support from the EU Horizon 2020 research and innovation programme and EFPIA.