title: Circulating Extracellular microRNA in Systemic Autoimmunity.
abstract: MicroRNAs (miRNAs) are differentially regulated in healthy, activated, inflamed, neoplastic, or otherwise pathological cells and tissues. While their main functions are executed intracellularly, many miRNAs can reproducibly be detected extracellularly in plasma and serum. This circulating, extracellular miRNA is protected against degradation by complexation with carrier proteins and/or by being enclosed in subcellular membrane vesicles. This, together with their tissue- and disease-specific expression, has fuelled the interest in using circulating microRNA profiles as harbingers of disease, i.e., as diagnostic analytes and as clues to dysregulated pathways in disease. Many studies show that inflammation and immune dysregulation, e.g., in autoimmune diseases, are associated with distinct miRNA expression changes in targeted tissues and in innate and adaptive immunity cells such as lymphocytes, natural killer cells, neutrophil granulocytes, and monocyte-macrophages. Exploratory studies (only validated in a few cases) also show that specific profiles of circulating miRNAs are associated with different systemic autoimmune diseases including systemic lupus erythematosus (SLE), systemic sclerosis, and rheumatoid arthritis. Even though the link between cellular alterations and extracellular profiles is still unpredictable, the data suggest that circulating miRNAs in autoimmunity may become diagnostically useful. Here, we review important circulating miRNAs in animal models of inflammation and in systemic autoimmunity and summarize some proposed functions of miRNAs in immune regulation and dysregulation. We conclude that the studies suggest new hypotheses and additional experiments, and that further diagnostic development is highly dependent on analytical method development and on obtaining sufficient numbers of uniformly processed samples from clinically well-characterized patients and controls.
authors.affiliation: Department of Autoimmunology and Biomarkers, Statens Serum Institut, Artillerivej 5, Bldg. 81, Rm. 419, 2300, Copenhagen S, Denmark. nhe@ssi.dk.|Department of Clinical Biochemistry and Pharmacology, Odense University Hospital, Odense C, Denmark. nhe@ssi.dk.
authors.forename: Niels H H
authors.initials: NHH
authors.lastname: Heegaard
authors.affiliation: Department of Congenital Disorders, Statens Serum Institut, Copenhagen S, Denmark.|Department of Autoimmunology and Biomarkers, Statens Serum Institut, Copenhagen S, Denmark.
authors.forename: Anting Liu
authors.initials: AL
authors.lastname: Carlsen
authors.affiliation: National Veterinary Institute, Technical University of Denmark, Lyngby, Denmark.
authors.forename: Kerstin
authors.initials: K
authors.lastname: Skovgaard
authors.affiliation: National Veterinary Institute, Technical University of Denmark, Lyngby, Denmark.
authors.forename: Peter M H
authors.initials: PMH
authors.lastname: Heegaard
keywords: Animal models; Autoimmune disease; Circulating microRNA; Immune system; Immunomodulation