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THU0289 Microrna signature in pediatric lupus nephritis: A pilot study
  1. P. Costa Reis1,2,
  2. P.A. Russo3,
  3. K.E. Sullivan2
  1. 1Pediatrics Department, Hospital De Santa Maria, Lisbon, Portugal
  2. 2Division of Allergy and Immunology
  3. 3Division of Pathology, Children’s Hospital of Philadelphia, Philadelphia, United States

Abstract

Background The development of high-throughput technologies for the global measurement of MicroRNAs (miRNAs), allowed these regulatory molecules to emerge as a new class of biomarkers in several diseases, including systemic lupus erythematosus (SLE).

miRNAs are noncoding RNAs, 18–25 nucleotides in length, responsible for post-transcriptional regulation. They play key roles in fundamental cellular processes such as proliferation, differentiation, apoptosis and metabolic homeostasis. miRNAs also exert control on the immune system, especially in the maintenance of immunological tolerance, participating on the regulation of T-cell selection in the thymus, B cell selection in germinal centers and on the development of regulatory T cells.

Altered miRNA expression can lead to dysregulation of multiple genes and broadly alter cell behavior. The study of miRNAs can, therefore, improve our understanding of the pathogenesis of rheumatologic diseases, including SLE.

Currently, the treatment and prognosis of lupus nephritis (LN) is still based on a histopathologic classification, which is an unreliable predictor of treatment response and disease outcome. miRNA studies performed on serum, urine and peripheral blood mononuclear cells have revealed distinct profiles in SLE patients. Further studies are necessary to identify a specific LN miRNA signature, which will bring new light to SLE pathogenesis and may lead to the finding of novel and much-required LN biomarkers.

Objectives The main aim of this exploratory study is to identify the miRNA signature of LN in children with juvenile-onset SLE (jSLE). The ultimate goal is to find miRNAs associated with disease activity and prognosis.

Methods A random selection of 6 patients with LN class III, IV and V, according to the International Society of Nephrology/Renal Pathology Society classification, was performed. As a control, normal tissue from a nephrectomy specimen was selected.

The formalin-fixed, paraffin-embedded (FFPE) kidney samples were used for miRNA extraction. RNA concentration and purity were measured using spectrophotometry.

The samples were processed using the nCounter® human miRNA assay kit, with direct digital detection of miRNAs through molecular barcodes. All samples were normalized within recommended guidelines for the miRNA count summation.

Results From over 700 human miRNAs analyzed, 5 were identified as being associated with LN: miR-16; miR-26a; miR-30b; miR-451and miR-494. In the first four, a significant decrease in expression was found in the kidneys from LN patients, most dramatically in class IV, when compared with class III and V. In the latter, the expression was higher in LN samples, with the highest level achieved in class V.

Conclusions miR-16, miR-26a, miR-30b, miR-451 and miR-494 were identified as components of the miRNA signature in kidneys of children with LN. These miRNAs are predicted to regulate the expression of genes that interfere with cell cycle, apoptosis and immune regulation, including CD80, IL18R1, CXCL16 and CCRL1. All of these have been implicated in the pathogenesis of nephritis and/or tissue inflammation.

These miRNAS might be associated with SLE pathogenesis and their function as LN biomarkers should be explored in further studies.

  1. Te J et al. PLoS ONE. 2010. 5(5):e10344.

  2. Wang G et al. Lupus. 2011. (20):493-500.

Disclosure of Interest None Declared

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