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Abstract: SA-OR043

Epigenetic Changes in Dendritic Cells in Patients with Systemic Lupus Erythematosus (SLE) with Renal Involvement

Session Information

Category: Glomerular Diseases

  • 1202 Glomerular Diseases: Immunology and Inflammation

Authors

  • Debska-Slizien, Alicja, Medical University of Gdansk, Gdansk, Poland
  • Komorniczak, Michal, Medical University of Gdansk, Gdansk, Poland
  • Wardowska, Anna, Medical University of Gdansk, Gdansk, Poland
  • Bullo-Piontecka, Barbara, Medical University of Gdansk, Gdansk, Poland
  • Trzonkowski, Piotr, Medical University of Gdansk, Gdansk, Poland
Background

SLE is a systemic autoimmune disease that affects the kidneys in about 50% of patients. The pathogenesis of lupus is still unclear and requires further research. There is a mounting evidence that changes in the dendritic cell (DC) function is associated with SLE development.

Methods

51 patients with lupus nephritis were enrolled to the project. The study group (SG) consisted of 9 men and 42 women, the average age was 44.05 (range: 21-69) years. The control group (CG) consisted of 22 people with no history of autoimmune diseases (5 male and 17 female) with average age 35 (range: 22-60) years.
Each participant of the study was cytometrically examined for DCs subpopulations (mDC - myeloid DC, pDC - plasmacytoid DC), including DC activity assessed. The global DNA methylation, histone H3 methylation was estimated. Cytokine profile analysis of both groups was performed with Luminex platform.

Results

In the SG as compare to CG, the percentage of DCs (HLA-DR+ Lin2-) was significantly lower (p=0.0259) and it was accompanied by a significant decrease in the CD123+ pDCs subpopulation (p=0.006). There were no statistical differences between the SG and CG in the mDCs (CD11c+) subpopulations (p=0.133). However, in the mDCs subpopulation a significant increase in the expression of activation markers was found in SG (for CD80+ p=0.002).
The study of epigenetic changes in DCs did not show significant differences in the global DNA methylation between groups. However, a statistically significant decrease in methylation histone H3K27me3 in mDCs was found in CG (p=0.0005), which suggests increasing transcriptional activity of DCs in this group. The strongest increase in activity was present in INF-inducible genes such as IRF8 (pDC p=0.0002; mDC p=0.037). In both subpopulations of DCs, the second strongly activated gene in patients with SLE was the TNF gene (pDC p=0.0049; mDC p=0.0198).
Changes in gene activity translate directly into the cytokine profile. The level of proinflammatory cytokines was statistically higher in SG: TNFα (p=0.0007), IL8 (p=0.0029).

Conclusion

DCs are vital factors in the pathogenesis of SLE. Epigenetic and transcriptomic studies of DCs and analysis of serum proteins have demonstrated their significant role in the genetic modification of the autoimmune process.

Funding

  • Government Support - Non-U.S.