Evaluation of survivin expression and regulating miRNAs of survivin expression in peripheral blood mononuclear cells in systemic lupus erythematous patients.

BACKGROUND: Systemic lupus erythematosus is a multisystemic rheumatic disease with different clinical features. Disturbance in apoptosis regulation seems to be a major factor in SLE development. OBJECTIVE: Survivin plays a key role in mitosis and inhibiting apoptosis. A study was conducted to examine the expression level of survivin and miRNAs that affect survivin transcript levels in patients with SLE. METHODS: We isolated peripheral blood mononuclear cells from 50 inactive SLE patients and 50 healthy controls. RNA is extracted and converted to cDNA. The quantitative real-time polymerase chain reaction is conducted to assess the expression levels of survivin total and its variants with effective miRNAs in PBMCs. RESULTS: Expression levels of miR-34a-5p (fold change = 1.5, p++ = 0.027), and 218-5p (fold change = 1.5, p++ = 0.020) were significantly increased. While miR-150-5p (fold change = 0.56, p++ = 0.003) was significantly decreased. The mRNA expression of survivin-WT (fold change = 0.63, p++ = 0.002) was significantly downregulated in SLE patients compared to the healthy controls. Survivin total and its two major variants (survivin-2B, and survivin-ΔEx3) did not differ significantly between SLE patients and controls. CONCLUSION: Although survivin-TS and its two variants (survivin-2B, and survivin-ΔEx3) were not differently expressed in SLE patients, survivin-WT had altered expression. Despite aberrant miRNA expression in PBMCs from SLE patients, survivin and miRNA expression were not associated with leukopenia. The pathogenesis of SLE disorder might be linked to survivin's other roles in the immune system aside from anti-apoptotic functions.

Role of the innate and adaptive immune responses in the pathogenesis of systemic lupus erythematosus.

OBJECTIVE: Systemic lupus erythematosus (SLE), the most common form of lupus, is a multisystemic rheumatic disease with different clinical features that generally affect women of childbearing age. The common symptoms of SLE are very similar to other autoimmune and non-autoimmune disorders, thereby it is known as a thousand faces disease. In this article, we are going to discuss some of the most updated information about immune system-related factors, cells, and cytokines involved in SLE pathogenesis. METHODS: Different electronic databases, especially PubMed/MEDLINE, Scopus, and Google Scholar, were searched to review and analyze relevant literature on the role of innate and adaptive immune cells and cytokines in the pathogenesis of SLE. A search for relevant literature was accomplished using various keywords including systemic lupus erythematosus, apoptosis, autoantibodies, immunopathogenesis of SLE, adaptive and innate immune cells, inflammatory cytokines, hormones, etc. RESULTS AND CONCLUSION: The most important characteristic of SLE is the production of antibodies against different nuclear autoantigens like double-strand DNA and RNA. The depositions of the immune complexes (ICs) that are generated between autoantibodies and autoantigens, along with aberrant clearance of them, can lead to permanent inflammation and contribute to tissue or organ damage. Related mechanisms underlying the initiation and development of SLE have not been clarified yet. Although, defects in immune tolerance, enhanced antigenic load, hyperactivity of T cells, and inappropriate regulation of B cells contribute to the pathogenic autoantibodies generation. Besides, sex hormones that influence the immune system seem to act as triggers or protectors of SLE development.