Session Information
Session Type: Abstract Submissions (ACR)
Background/Purpose:
New biomarkers to guide clinical management of lupus nephritis (LN) patients are highly desirable, since the histopathologic classification currently in use is an unreliable predictor of treatment response and disease outcome. MicroRNAs have emerged as a new class of biomarkers in several rheumatic diseases, but their role in LN is still unclear. These noncoding RNAs have a post-transcriptional regulatory effect, playing a key role in fundamental cellular processes and influencing immunologic function, especially in the maintenance of immunological tolerance. Perturbations in the microRNA expression patterns can, therefore, lead to pathological conditions, including autoimmune diseases, like systemic lupus erythematosus (SLE).
MicroRNA studies performed on serum, urine and peripheral blood mononuclear cells have revealed distinct profiles in SLE patients. Further studies are thus necessary to identify a specific LN microRNA signature, which will illuminate SLE pathogenesis and may lead to novel LN biomarkers.
The main aim of this study is to identify the microRNA signature in kidneys of children with LN. The ultimate goal is to find microRNAs associated with disease activity and prognosis that may guide clinical practice.
Methods:
Paraffin-embedded tissue samples from children with LN, kidney biopsies performed on kidney donors, and post-streptococcal glomerulonephritis were used for microRNA extraction with Quiagen™ miRNeasy kit. Direct digital detection of microRNAs, through molecular barcodes, was performed with the nCounter® human miRNA assay kit.
Results:
The microRNA signature can clearly differentiate samples from normal kidneys of those affected with LN. From over 700 human microRNAs analyzed, miR-26a and miR-30b were identified as being associated with pediatric LN. A significant decrease in the expression of these microRNAs was found in LN class IV, when compared to normal tissue, post-streptococcal glomerulonephritis, LN class III or LN class V.
Conclusion:
An altered microRNA signature can lead to the dysregulation of gene expression and broadly alter cell behavior. The study of microRNAs can, therefore, improve our understanding of the pathogenesis of several diseases. With this project, miR-26a and miR-30b were identified for the first time as components of the microRNA signature in kidneys of children with LN. These microRNAs are predicted to regulate the expression of genes that interfere with cell cycle, apoptosis and immune regulation, including IL18R1, which has been implicated in the pathogenesis of nephritis and tissue inflammation and HDAC9, which acts as an epigenetic switch in effector T cell-mediated systemic autoimmunity. This study has provided new insights for LN pathogenesis and for the development of new biomarkers.
Disclosure:
P. Costa Reis,
None;
P. Russo,
None;
K. E. Sullivan,
None.
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ACR Meeting Abstracts - https://acrabstracts.org/abstract/pediatric-lupus-nephritis-micrornas-macro-inflammation/