Background/Purpose: Systemic lupus erythematosus (SLE) is an autoimmune disease that primarily affects women, and is associated with periods of elevated and suppressed clinical symptoms. SLE prevalence varies between ethnic groups, with  African American women having higher rates and increased disease severity. Understanding how dysregulated immune pathways associate with disease activity within different ethnic groups is critical for optimizing effective and personalized treatment options for SLE.

Methods: Plasma cytokine levels of European or African American healthy controls (n=18) and SLE patients with either higher (SLEDAI≥4) (n=20) or lower (SLEDAI<4) (n=20) disease activity were assessed by 37-plex xMAP assays and ELISAs. Further, peripheral whole blood samples collected from subjects were stimulated for 24 hours with either PMA and ionomycin, PHA and ionomycin or Toll-like receptor (TLR) ligands TLR4, TLR7/8 andTLR9 for cytokine analysis of cell culture supernatants. All SLE patients met ACR classification criteria.

Results: Plasma levels of SCF (p=0.0051), sICAM-1 (p=0.0097), TNFa (p=0.0302), BLyS (p=0.0312), and IL-1RA (p=0.0422) were higher in African American SLE patients compared to European American SLE patients, whereas eotaxin (p=0.0055) was only higher in European American patients (Figure 1). In European American SLE patients with higher disease activity, SCF and sICAM-1 (p<0.05) were elevated compared to SLE patients with lower disease activity. African American SLE patients with higher disease activity were distinguished from lower disease activity patients by elevated levels of MCP-1 (p=.0048), eotaxin (p=0.029), IL-7 (p=0.03), IL-9 (p=0.041 and CXCL13 (p=0.032). Following TLR stimulation, SLE patients with higher disease activity had a reduced fold change in most soluble mediators compared to SLE patients with lower disease activity and healthy controls, specifically with Type I and II IFN and IFN associated cytokines (p<0.05). This is likely due to the cell pathways being previously activated before stimulation. In addition, European American higher disease activity patients were distinguished from African American SLE patients by a higher fold change in IL-10 (p=0.0068) and IL-1RA (p=0.045) following TLR stimulation. African American patients were characterized by a higher fold change in most soluble mediators following PMA and ionomycin stimulation, whereas only the fold change in IL-10 (p=0.023) was higher in European American controls compared to patients.

Conclusion: Elevated soluble mediators contribute to heightened disease activity that is influenced by race with African American SLE patients having higher levels of pro-inflammatory cytokines and less involvement of regulatory pathways compared to European American patients.