Session Type: ACR Concurrent Abstract Session
Session Time: 4:30PM-6:00PM
Background/Purpose: High dose corticosteroids such as cyclophosphamide are commonly used to treat lupus nephritis (LN). Although effective in preventing end stage renal disease (ESRD) in most cases, significant long-term side effects such as infections, increased risk of malignancy, and infertility are common and are related to the duration of therapy or the cumulative dose of medications. These side effects could be mitigated via a personalized medicine approach, if an individual’s response to treatment could be predicted. However there are currently no markers that can reliably determine response or refractoriness to treatment at an individual level. MicroRNAs (miRNAs), a class of small, non-coding RNAs responsible for post-transcriptional regulation, have been shown to have altered expression levels in a variety of diseases suggesting their potential use as diagnostic, prognostic, and treatment response biomarkers. We propose miRNAs can be appropriate predictive markers for response to cyclophosphamide treatment.
Methods: <span”>RNA was isolated and analyzed via TaqMan® Array MicroRNA 384-well Cards, from formalin-fixed paraffin embedded (FFPE) renal biopsies of two unique cohorts of patients with LN who were subsequently treated with cyclophosphamide and had at least 2 years of follow up history. Patients who responded to cyclophosphamide based on urinalysis criteria of no active urinary sediments, no RBCs and/or WBCs in urine, and proteinuria less than 1 gram were classified as responders while those that did not fit the criteria were classified as non-responders. The first cohort was composed of 32 patients with 17 responders and 15 non-responders, while the second cohort (the validation cohort) contained 39 patients with 22 responders and 17 non-responders. Significantly differentially expressed miRNAs, determined via 2-ΔΔCtmethod, from the first cohort were validated by the second cohort. Potential target mRNAs for candidate miRNAs were determined through miRDB, TarBase, RNA22, and Ingenuity Pathway Analysis (IPA) databases. Predicted targets were further analyzed for disease activity and nephrotoxicity through IPA.
Results: Six significantly up-regulated miRNAs, hsa-miR-30c-2-3p, hsa-miR-29b-1-5p, hsa-miR-195-3p, hsa-miR-424-3p, hsa-miR-1260a, and hsa-miR-1248 were found in responders. Analysis of miRNA targets generated by four prediction algorithms revealed immunological disease specificity and renal involvement.
Conclusion: These miRNAs may act as prognostic markers of renal outcomes and treatment response, which can establish a more personalized treatment of lupus nephritis in the future. As our next step we will attempt further validation of these miRNAs in serum and urine of patients with lupus nephritis.
To cite this abstract in AMA style:Hadavand M, Binmadi N, Zhou H, Tandon M, Hasni S, Alevizos I. Identification of Microrna Predictive of Outcome in Lupus Nephritis [abstract]. Arthritis Rheumatol. 2016; 68 (suppl 10). https://acrabstracts.org/abstract/identification-of-microrna-predictive-of-outcome-in-lupus-nephritis/. Accessed May 22, 2019.
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