FRI0005 The relationship between juvenile systemic lupus erythematosus and the transcription factors nf-kappab and ppar-gamma
Authors: S. Sahin, S. Durmus, A. Adrovic, K. Barut, R. Gelisgen, H. Uzun, O. Kasapcopur
Journal: Annals of the Rheumatic Diseases (2018)

<h3>Background</h3> Systemic lupus erythematosus (SLE) is an autoimmune disease characterised by high-levels of autoantibodies mainly targeting nuclear antigens and loss of self-tolerance. Peroxisome-proliferator activated receptor gamma (PPARγ) and nuclear factor-kappa beta (NF-κB) are transcription factors, which, within normal levels, have shown to be crucial in immunomodulation namely, activation and development of normal lymphocytes, negative and positive selection of T and B cells. High-levels of NF-κB has inflammatory properties such as release of autoreactive T cells. On the contrary, PPARγ has anti-inflammatory effects, which has been demonstrated to be effective when used early in prevention of disease in murine models of systemic lupus erythematosus. <h3>Objectives</h3> Herein, we investigated whether NF-κB and PPARγ could exert opposite effects in the immune response and the possible implications in immunomodulation of juvenile systemic lupus erythematosus. <h3>Methods</h3> Serum NF-κB and PPARγ levels were measured in 42 juvenile systemic lupus erythematosus. In addition,19 juvenile systemic sclerosis and 25 age-matched healthy children were selected for patient control and healthy control, respectively. We have also assessed the relation of these transcription factors with disease activity and anti-ds DNA. <h3>Results</h3> The control group did not differ from the juvenile SLE and juvenile systemic sclerosis patients for age (p&gt;0.05). According to our study, serum NF-κB levels of juvenile SLE and juvenile systemic sclerosis patients were significantly higher (1.87±1.0 and 2.17±1.0 versus 1.25±0.7), while serum PPARγ levels were significantly lower than that of healthy controls (1.58±0.6 and 1.52±0.5 versus 2.03±0.9). The difference was not significant between juvenile systemic lupus erythematosus and juvenile systemic sclerosis. In patients with juvenile systemic sclerosis serum NF-κB levels negatively correlated with serum PPARγ levels (R=−0.49; p=0.032); however, this relationship was not observed in juvenile SLE patients and healthy controls. <h3>Conclusions</h3> Increased serum NF-κB levels represent upregulated signalling cascades, so it is associated with increased levels of pro-inflammatory cytokines. Since juvenile systemic sclerosis and juvenile systemic lupus erythematosus are autoimmune diseases, patients had high levels of NF-κB and low levels of PPAR than controls, as expected. Previous studies revealed that PPARγ activation inhibits NF-κB transcriptional activity. Correlation results in juvenile systemic sclerosis cohort are compatible with this finding, however not in juvenile systemic lupus erythematosus patients. This could be due to the limited number of patients. Further studies with large number of patients are needed to better elucidate the implication of these transcription factors in therapeutic pathways. <h3>References</h3> [1] Zubair A, Frieri M. NF-κB and systemic lupus erythematosus: examining the link. J Nephrol2013;26(6):953–9. [2] Hayden MS, Ghosh S. NF-κB, the first quarter-century: Remarkable progress and outstanding questions. Genes Dev2012;26(3):203–234. [3] Aprahamian TR, Bonegio RG, Weitzner Z, et al. Peroxisome proliferator-activated receptor gamma agonists in the prevention and treatment of murine systemic lupus erythematosus. Immunology2014;142(3):363–73. <h3>Disclosure of Interest</h3> None declared