Abstract
Systemic lupus erythematosus (SLE) is a serious autoimmune disease with variety of organ manifestations. The most dreadful one, affecting the majority of SLE patients, is kidney manifestation—lupus nephritis (LN). Dendritic cells (DC) are believed to be one of the culprits of immune dysregulation in LN. Flow cytometry analysis was applied to identify the frequency and activity of peripheral blood DCs subpopulations: myeloid and plasmacytoid, in LN patients. Magnetically isolated mDCs and pDCs were subjected to molecular analysis of genes expression, evaluation of global DNA methylation and histone H3 methylation. We observed distinctive features of DCs associated with the stages of nephritis in LN patients. Lower numbers of pDCs were observed in patients with severe LN, while increased co-stimulatory potential of mDCs was connected with the early, mild stage of this disease. IRF1 transcript upregulation was specific for mDCs from total LN patients, while exceptional amount of IRF1 mRNA was detected in mDCs from severe LN patients. DCs DNA hypermethylation seemed characteristic for severe LN, whereas a decrease in H3K4me3 and H3K27me3 marks was significant for the early stages of LN. These findings present dendritic cell alterations that may reflect renal involvement in SLE, laying foundations for new strategy of diagnosis and monitoring of LN patients, omitting invasive kidney biopsies.
Highlights
Autoimmunity refers to abnormalities in the activity and function of the immune system leading to the deleterious effect of a loss of tolerance to self-antigens
The incidence and severity of renal involvement varies between patients with systemic lupus erythematosus (SLE), but seems to be ethnicity associated, as African-American, Asian or Hispanic patients are more likely to develop end-stage kidney disease compared to European-American lupus patients [4]
We focused on gene expression patterns in lupus nephritis patients divided into groups based on the severity of chronic kidney disease
Summary
Autoimmunity refers to abnormalities in the activity and function of the immune system leading to the deleterious effect of a loss of tolerance to self-antigens. The incidence and severity of renal involvement varies between patients with SLE, but seems to be ethnicity associated, as African-American, Asian or Hispanic patients are more likely to develop end-stage kidney disease compared to European-American lupus patients [4]. There is a constant and critical need to elucidate immune mechanism behind LN, in order to identify new and evaluated biomarkers facilitating precise diagnosis and patients monitoring. This would inevitably lead to the development of more effective and tailored therapies with better outcomes and fewer side effects. The innate immunity cells, especially dendritic cells (DCs), have moved to the fore, due to their natural ability to establish and maintain peripheral tolerance [2, 8]
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