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Abstract
Background Cytokine dysregulation contributes to immune dysfunction, inflammation and organ damage in Systemic Lupus Erythematosus (SLE). Cytokines have multifarious interactions on other cytokines and immune cells. Thus cytokines studies should reflect this intrinsic complexity.
Aim Utilise Principle Component Analysis (PCA) to unravel the interplay of a selection of cytokines for SLE versus healthy controls.
Methods A cross-sectional study of 102 SLE patients and 30 controls. Sera samples of IFN-γ, IL-1β, IL-4, IL-6, IL-10, IL-12, IL17, BAFF and MCP-1, were analysed by ELISA and compared non-parametrically between groups. SLE disease activity was assessed by SLEDAI-2K. PCA demonstrated the cytokine profiles of healthy controls, SLE patients with low (SLEDAI-2K<3) and moderate to high disease activity (SLEDAI-2K≥3).
Results BAFF correlated with disease activity (Rs. 0.483, p<0.001) and highest in SLEDAI-2K≥3 (p<0.001). BAFF was not in the Principal Component 1 (PC1) of any group (−0.22 vs −0.18 vs 0.06) (Figures 2 and 3).
IL-1β was inversely correlated with disease activity (Rs. −0.216, p=0.013) and lowest in SLEDAI-2K≥3 (p=0.001). IL-1β was a moderate driver of cytokine variance for healthy controls, but became more dominant across SLEDAI-2K<3 and SLEDAI-2K≥3, i.e. PC1 (0.59 vs 0.976 vs 0.985).
Median serum levels of cytokines (pg/mL) in Controls and SLE patients with SLEDAI-2K<3 and SLEDAI-2K≥3. IQR; Interquartile range.
Mean serum levels (pg/mL) of cytokines in heathly controls and SLE patients.
Principal Component Analysis of Controls vs SLEDAI<3 group.
Principal Component Analysis of Controls vs SLEDAI≥3 group.
Conclusions Increased BAFF levels were not a direct agitator of cytokine variation in SLE, suggesting a contribution to disease activity through other pathways. In contrast, the reduction of IL-1β had a dominant effect on cytokine variance in SLE (PC 1). Principal component analysis is a useful asset for cytokine profiling in SLE.