Distinct Cytokine Profiles in Lupus Low Disease Activity State Subgroups Identify Patients at Risk for Disease Flare

Area of Science:

• Immunology
• Rheumatology
• Systems Biology

Background:

• Systemic lupus erythematosus (SLE) patients in low disease activity state (LLDAS) can still experience flares.
• Understanding cytokine profiles in LLDAS subgroups is crucial for predicting disease activity and flares.

Purpose of the Study:

• To compare cytokine profiles between clinically active (CA) and serologically active clinically quiescent (SACQ) LLDAS subgroups.
• To identify predictors of disease flare in patients with SLE maintained in LLDAS.

Main Methods:

• Weighted gene co-expression network analysis to identify cytokine modules.
• Correlation analysis between cytokine modules and clinical traits.
• Cox regression analysis to identify flare predictors.

Main Results:

• Three cytokine modules were identified, with brown and turquoise modules correlating with clinical assessments.
• Interleukin-6 (IL-6) and IL-8 levels were higher in the CA subgroup compared to SACQ.
• Non-sustained LLDAS and elevated IL-6 (≥ 45.1 pg/mL) independently predicted flares (HR 8.73 and 10.4, respectively).

Conclusions:

• Cytokine elevation persists in SLE patients even when in LLDAS.
• Maintaining LLDAS and monitoring IL-6 levels are important for predicting and potentially preventing disease flares.