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Whole blood microRNA expression pattern differentiates patients with rheumatoid arthritis, their seropositive first-degree relatives, and healthy unrelated control subjects

Authors
  • Anaparti, Vidyanand1, 2, 3
  • Smolik, Irene1, 3, 4
  • Meng, Xiaobo1, 2, 3
  • Spicer, Victor2
  • Mookherjee, Neeloffer1, 2, 5
  • El-Gabalawy, Hani1, 2, 3, 4, 5
  • 1 University of Manitoba, Department of Internal Medicine, Rady Faculty of Health Sciences, Room 799, 715 McDermot Avenue, Winnipeg, MB, R3E 3P4, Canada , Winnipeg (Canada)
  • 2 University of Manitoba, Manitoba Centre for Proteomics and Systems Biology, Winnipeg, MB, Canada , Winnipeg (Canada)
  • 3 University of Manitoba, Rheumatic Diseases Unit, Winnipeg, MB, Canada , Winnipeg (Canada)
  • 4 University of Manitoba, Division of Rheumatology, Faculty of Health Sciences, Winnipeg, MB, Canada , Winnipeg (Canada)
  • 5 University of Manitoba, Department of Immunology, Rady Faculty of Health Sciences, Winnipeg, MB, Canada , Winnipeg (Canada)
Type
Published Article
Journal
Arthritis Research & Therapy
Publisher
BioMed Central
Publication Date
Nov 10, 2017
Volume
19
Issue
1
Identifiers
DOI: 10.1186/s13075-017-1459-x
Source
Springer Nature
Keywords
License
Green

Abstract

BackgroundEpigenetic mechanisms can integrate gene-environment interactions that mediate disease transition from preclinical to clinically overt rheumatoid arthritis (RA). To better understand their role, we evaluated microRNA (miRNA, miR) expression profile in indigenous North American patients with RA who were positive for anticitrullinated protein antibodies; their autoantibody-positive, asymptomatic first-degree relatives (FDRs); and disease-free healthy control subjects (HCs).MethodsTotal RNA was isolated from whole blood samples obtained from HC (n = 12), patients with RA (n = 18), and FDRs (n = 12). Expression of 35 selected relevant miRNAs, as well as associated downstream messenger RNA (mRNA) targets of miR-103a-3p, was determined by qRT-PCR.ResultsWhole blood expression profiling identified significantly differential miRNA expression in patients with RA (13 miRNAs) and FDRs (10 miRNAs) compared with HCs. Among these, expression of miR-103a-3p, miR-155, miR-146a-5p, and miR-26b-3p was significantly upregulated, whereas miR-346 was significantly downregulated, in both study groups. Expression of miR-103a-3p was consistently elevated in FDRs at two time points 1 year apart. We also confirmed increased miR-103a-3p expression in peripheral blood mononuclear cells from patients with RA compared with HCs. Predicted target analyses of differentially expressed miRNAs in patients with RA and FDRs showed overlapping biological networks. Consistent with these curated networks, mRNA expression of DICER1, AGO1, CREB1, DAPK1, and TP53 was downregulated significantly with miR-103a-3p expression in FDRs.ConclusionsWe highlight systematically altered circulating miRNA expression in at-risk FDRs prior to RA onset, a profile they shared with patients with RA. Prominently consistent miR-103a-3p expression indicates its utility as a prognostic biomarker for preclinical RA while highlighting biological pathways important for transition to clinically detectable disease.

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