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J Immunol. 2016 Oct 1;197(7):2854-63. doi: 10.4049/jimmunol.1601142. Epub 2016 Aug 17.

Blood-Borne RNA Correlates with Disease Activity and IFN-Stimulated Gene Expression in Systemic Lupus Erythematosus.

Author information

1
Resolve Therapeutics, LLC, Seattle, WA 98103;
2
EA Genomics/Q Solutions, Durham, NC 27703;
3
PlasmaLab International, Everett, WA 98201;
4
Sage Bionetworks, Seattle, WA 98109;
5
Benaroya Research Institute, Seattle, WA 98101;
6
Swedish Medical Center and University of Washington, Seattle, WA 98122;
7
University of California, San Francisco, San Francisco, CA 94143;
8
The Feinstein Institute for Medical Research, Manhasset, NY 11030;
9
College of Human Medicine, Michigan State University, East Lansing, MI 48824;
10
Metroplex Clinical Research Center, Dallas, TX 75231;
11
Altoona Center for Clinical Research, Duncansville, PA 16635;
12
Benaroya Research Institute, Seattle, WA 98101; Sidra Medical and Research Center, Doha, Qatar; and.
13
Department of Rheumatology, University of Washington, Seattle, WA 98109.
14
Resolve Therapeutics, LLC, Seattle, WA 98103; jp@resolvebio.com.

Abstract

The loss of tolerance and the presence of circulating autoantibodies directed against nuclear Ags is the hallmark of systemic lupus erythematosus (SLE). Many of these Ags are complexed with short, noncoding RNAs, such as U1 and Y1. The amount of U1 and Y1 RNA complexed with SLE patient Abs and immune complexes was measured in a cross-section of 228 SLE patients to evaluate the role of these RNA molecules within the known biochemical framework of SLE. The study revealed that SLE patients had significantly elevated levels of circulating U1 and/or Y1 RNA compared with healthy volunteers. In addition, the blood-borne RNA molecules were correlated with SLE disease activity and increased expression of IFN-inducible genes. To our knowledge, this study provides the first systematic examination of the role of circulating RNA in a large group of SLE patients and provides an important link with IFN dysregulation.

PMID:
27534558
DOI:
10.4049/jimmunol.1601142
[Indexed for MEDLINE]
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