Gene-Specific DNA Methylation Changes Predict Remission in Patients with ANCA-Associated Vasculitis

ANCA-associated vasculitis is an autoimmune condition characterized by vascular inflammation and organ damage. Pharmacologically induced remission of this condition is complicated by relapses. Potential triggers of relapse are immunologic challenges and environmental insults, both of which associate...

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Published in:Journal of the American Society of Nephrology 2017-04, Vol.28 (4), p.1175-1187
Main Authors: Jones, Britta E, Yang, Jiajin, Muthigi, Akhil, Hogan, Susan L, Hu, Yichun, Starmer, Joshua, Henderson, Candace D, Poulton, Caroline J, Brant, Elizabeth J, Pendergraft, 3rd, William F, Jennette, J Charles, Falk, Ronald J, Ciavatta, Dominic J
Format: Article
Language:English
Subjects:
Anti-Neutrophil Cytoplasmic Antibody-Associated Vasculitis - genetics
Autoantigens - genetics
Basic Research
DNA Methylation
Female
Gene Expression Regulation
Humans
Male
Middle Aged
Myeloblastin - genetics
Peroxidase - genetics
Prognosis
Remission Induction
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Summary:ANCA-associated vasculitis is an autoimmune condition characterized by vascular inflammation and organ damage. Pharmacologically induced remission of this condition is complicated by relapses. Potential triggers of relapse are immunologic challenges and environmental insults, both of which associate with changes in epigenetic silencing modifications. Altered histone modifications implicated in gene silencing associate with aberrant autoantigen expression. To establish a link between DNA methylation, a model epigenetic gene silencing modification, and autoantigen gene expression and disease status in ANCA-associated vasculitis, we measured gene-specific DNA methylation of the autoantigen genes myeloperoxidase ( ) and proteinase 3 ( ) in leukocytes of patients with ANCA-associated vasculitis observed longitudinally ( =82) and of healthy controls ( =32). Patients with active disease demonstrated hypomethylation of and and increased expression of the autoantigens; in remission, DNA methylation generally increased. Longitudinal analysis revealed that patients with ANCA-associated vasculitis could be divided into two groups, on the basis of whether DNA methylation increased or decreased from active disease to remission. In patients with increased DNA methylation, and expression correlated with DNA methylation. Kaplan-Meier estimate of relapse revealed patients with increased DNA methylation at the promoter had a significantly greater probability of a relapse-free period (
ISSN:1046-6673
1533-3450
DOI:10.1681/ASN.2016050548