title: Epigenetics and Vasculitis: a Comprehensive Review.
abstract: Vasculitides represent a group of relatively rare systemic inflammatory diseases of the blood vessels. Despite recent progress in understanding the genetic basis and the underlying pathogenic mechanisms in vasculitis, the etiology and pathogenesis of vasculitis remain incompletely understood. Epigenetic dysregulation plays an important role in immune-mediated diseases, and the contribution of epigenetic aberrancies in vasculitis is increasingly being recognized. Histone modifications in the PR3 and MPO gene loci might be mechanistically involved in the pathogenesis of anti-neutrophil cytoplasmic antibody (ANCA)-associated vasculitis. Similarly, other studies revealed important epigenetic contribution to other vasculitides, including Kawasaki disease and IgA vasculitis. More recently, genome-wide epigenomic studies have been performed in several vasculitides. A recent genome-wide DNA methylation study uncovered an important role for epigenetic remodeling of cytoskeleton-related genes in the pathogenesis of Behçet's disease and suggested that reversal of some of these DNA methylation changes associates with disease remission. Genome-wide DNA methylation profiling characterized the inflammatory response in temporal artery tissue from patients with giant cell arteritis and showed increased activation of calcineurin/nuclear factor of activated T cells (NFAT) signaling, prompting the suggestion that a specific calcineurin/NFAT inhibitor that is well tolerated and with the added beneficial anti-platelet activity, such as dipyridamole, might be of therapeutic potential in giant cell arteritis. While epigenetic studies in systemic vasculitis are still in their infancy, currently available data clearly indicate that investigating the epigenetic mechanisms underlying these diseases will help to better understand the pathogenesis of vasculitis and provide novel targets for the development of disease biomarkers and new therapies.
authors.affiliation: Division of Rheumatology, Department of Internal Medicine, University of Michigan, Ann Arbor, MI, USA.
authors.forename: Paul
authors.initials: P
authors.lastname: Renauer
authors.affiliation: Division of Rheumatology, Department of Internal Medicine, University of Michigan, Ann Arbor, MI, USA.
authors.forename: Patrick
authors.initials: P
authors.lastname: Coit
authors.affiliation: Division of Rheumatology, Department of Internal Medicine, University of Michigan, Ann Arbor, MI, USA. asawalha@umich.edu.|Center for Computational Medicine and Bioinformatics, University of Michigan, Ann Arbor, MI, USA. asawalha@umich.edu.|, 5520 MSRB-1, SPC 5680, 1150 W. Medical Center Drive, Ann Arbor, MI, 48109, USA. asawalha@umich.edu.
authors.forename: Amr H
authors.initials: AH
authors.lastname: Sawalha
mesh_terms: D000818:Animals; D019268:Antibodies, Antineutrophil Cytoplasmic / Q000276:immunology; D018899:CpG Islands; D019175:DNA Methylation; D044127:Epigenesis, Genetic; D005786:Gene Expression Regulation; D020022:Genetic Predisposition to Disease; D006657:Histones / Q000378:metabolism; D006801:Humans; D007070:Immunoglobulin A / Q000276:immunology; D035683:MicroRNAs / Q000235:genetics; D015398:Signal Transduction; D014657:Vasculitis / Q000175:diagnosis / Q000235:genetics* / Q000276:immunology / Q000378:metabolism
chemical_list: D019268:Antibodies, Antineutrophil Cytoplasmic; D006657:Histones; D007070:Immunoglobulin A; D035683:MicroRNAs
keywords: DNA methylation; Epigenetics; Histone modification; Vasculitis; miRNA