Interplay of NF-κB and PPAR-γ transcription factors in patients with juvenile systemic lupus erythematosus

Objective Juvenile SLE (jSLE) is an autoimmune disease characterised by the presence of high levels of autoantibodies, predominantly targeting nuclear antigens, resulting in a breakdown of self-tolerance. However, its pathogenesis is multifactorial and poorly understood. The aim of this study was to evaluate the potential of nuclear factor-kappa B (NF-κB) and peroxisome proliferator-activated receptor-gamma (PPAR-γ) as biomarkers for jSLE. Methods In this study, serum NF-κB and PPAR-γ levels were determined by immunoassay in 42 patients with jSLE. In addition, 19 juvenile systemic sclerosis (jSSc) and 25 age-matched healthy children were selected as patient control and healthy control, respectively. Results Serum NF-κB levels in patients with jSLE demonstrated a positive trend towards elevation compared with the controls with no significant difference (p=0.030). In addition, serum NF-κB levels in patients with jSSc were significantly higher than that of the healthy controls (p=0.005). Serum PPAR-γ levels were tend to be lower in both patients with jSLE and jSSc compared with the controls, with no significant difference. Specifically, NF-κB levels were significantly higher in patients with jSLE with cumulative damage (PedSDI≥1) compared with those without, at p=0.044. Logistic regression showed that PPAR-γ levels lower than 2.42 ng/mL were associated with the development of jSLE (OR 7.59) and lower than 2.16 ng/mL for jSSc (OR 10.90). The combined high levels of NF-κB with low PPAR-γ increased the risk of developing jSSc by 21.33-fold. Conclusions The observed trend of elevated NF-κB levels and decreased PPAR-γ levels in our study suggests their potential as biomarkers associated with increased proinflammatory signalling in jSLE and jSSc. However, our findings must be regarded as hypothesis-generating and confirmed in larger datasets. Moreover, their roles in monitoring the course of a disease and guiding therapeutic strategies in juvenile systemic autoimmune diseases need to be clearly investigated. Further extension of these findings may lead to better management and improvement in the outcomes of such patients.