ACR Meeting Abstracts

ACR Meeting Abstracts

Abstract Number: 1074

DNA Methylation Patterns in Naïve CD4+ T Cells Identify Epigenetic Susceptibility Loci for Malar Rash and Discoid Rash in Systemic Lupus Erythematosus

Paul Renauer1, Patrick Coit1, Matlock A. Jeffries2, Joan T. Merrill3, W Joseph McCune4, Kathleen Maksimowicz-McKinnon5 and Amr H. Sawalha6, 1Division of Rheumatology, University of Michigan, Ann Arbor, MI, 2Rheumatology, University of Oklahoma Health Sciences Center, Oklahoma City, OK, 3Oklahoma Medical Research Foundation, Oklahoma City, OK, 4Int Med/ Rheum, University of Michigan, Ann Arbor, MI, 5Rheumatology, Henry Ford Hospital, Detroit, MI, 6Rheumatology, University of Michigan, Ann Arbor, MI

Meeting: 2015 ACR/ARHP Annual Meeting

Date of first publication: September 29, 2015

Keywords: , , ,

Session Information

Date: Sunday, November 8, 2015

Title: Systemic Lupus Erythematosus - Human Etiology and Pathogenesis: Genetics, Gene Expression, and Epigenetics

Session Type: ACR Concurrent Abstract Session

Session Time: 4:30PM-6:00PM

Background/Purpose: Systemic lupus erythematosus (SLE) is a complex autoimmune disease characterized by heterogeneous clinical manifestations, autoantibody production, and epigenetic dysregulation in T cells. We sought to investigate the epigenetic contribution to the development of cutaneous manifestations in SLE.

Methods: We performed genome-wide DNA methylation analyses in SLE patients stratified by a history of malar rash, discoid rash, or neither cutaneous manifestation, and age, sex, and ethnicity matched healthy controls. We characterized differentially methylated regions (DMRs) in naïve CD4+ T cells in each disease subset, and assessed functional relationships between DMRs using bioinformatic approaches.

Results: We identified 36 and 37 unique DMRs that contribute to the epigenetic susceptibility to malar rash and discoid rash, respectively. These DMRs were primarily localized to genes mediating cell proliferation and apoptosis. Hypomethylation of MIR886 and TRIM69, and hypermethylation of RNF39 were specific to lupus patients with a history of malar rash. Hypomethylation of the cytoskeleton-related gene RHOJ was specific to SLE patients with a history of discoid rash. In addition, discoid rash-specific hypomethylated DMRs were found in genes involved in antigen-processing and presentation such as TAP1 and PSMB8. Network analyses showed that DMRs in SLE patients with but not without a history of cutaneous manifestations are associated with TAP-dependent processing and MHC-class I antigen cross-presentation (P = 3.66×10-18 in malar rash, and 3.67×10-13 in discoid rash).

Conclusion: We characterized DNA methylation changes in naïve CD4+ T cells specific to malar rash and discoid rash in patients with SLE. These data suggest unique epigenetic susceptibility loci that predispose to or are associated with the development of cutaneous manifestations in SLE.

Disclosure: P. Renauer, None; P. Coit, None; M. A. Jeffries, None; J. T. Merrill, None; W. J. McCune, None; K. Maksimowicz-McKinnon, None; A. H. Sawalha, None.

To cite this abstract in AMA style:

Renauer P, Coit P, Jeffries MA, Merrill JT, McCune WJ, Maksimowicz-McKinnon K, Sawalha AH. DNA Methylation Patterns in Naïve CD4+ T Cells Identify Epigenetic Susceptibility Loci for Malar Rash and Discoid Rash in Systemic Lupus Erythematosus [abstract]. Arthritis Rheumatol. 2015; 67 (suppl 10). https://acrabstracts.org/abstract/dna-methylation-patterns-in-naive-cd4-t-cells-identify-epigenetic-susceptibility-loci-for-malar-rash-and-discoid-rash-in-systemic-lupus-erythematosus/. Accessed .

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