ACR Meeting Abstracts

ACR Meeting Abstracts

Abstract Number: 1620

DNA Methylation Profiling of Rheumatoid Arthritis Peripheral Blood Identifies Hypermethylation of TRIM69 Promoter Region in CD4+ T Cells Associated with Disease Activity

Amanda Mok1, Brooke Rhead1, Calliope Holingue1, Xiaorong Shao1, Diana Quach1, Hong L. Quach1, Elizabeth Sinclair2, Jonathan D. Graf3, Thomas M. Link4, Ruby Harrison3, Vladimir Chernitskiy3, Wei Wang5, Gary S. Firestein6, Lisa F. Barcellos1 and Lindsey A. Criswell3, 1Genetic Epidemiology and Genomics Laboratory, University of California, Berkeley, Berkeley, CA, 2Division of Laboratory Medicine, University of California, San Francisco, San Francisco, CA, 3Rosalind Russell / Ephraim P. Engleman Rheumatology Research Center, University of California, San Francisco, San Francisco, CA, 4Department of Radiology and Biomedical Imaging, Musculoskeletal Quantitative Imaging Research, UCSF, San Francisco, CA, 5Chemistry and Biochemistry, University of California, San Diego, La Jolla, CA, 6Division of Rheumatology, Allergy and Immunology, University of California, San Diego, La Jolla, CA

Meeting: 2015 ACR/ARHP Annual Meeting

Date of first publication: September 29, 2015

Keywords: , ,

Session Information

Date: Monday, November 9, 2015

Title: Rheumatoid Arthritis - Human Etiology and Pathogenesis Poster II

Session Type: ACR Poster Session B

Session Time: 9:00AM-11:00AM

Background/Purpose: Epigenetic modifications have been previously associated with rheumatoid arthritis (RA [MIM 180300]). This study aimed to determine whether differential DNA methylation in peripheral blood samples is associated with disease activity among RA patients.

Methods: Peripheral blood samples were taken from 59 RA patients in the University of California, San Francisco RA cohort (all satisfied ACR classification criteria; 53 were seropositive; 41 had evidence of erosive disease). Cells were FACS-sorted into 4 immune cell subsets (CD14+ monocytes, CD19+ B cells, CD4+ memory T cells, CD4+ naïve T cells) per individual, and 233 epigenome-wide DNA methylation profiles were generated using Illumina HumanMethylation450 BeadChips. Patients were also evaluated with the Clinical Disease Activity Index (CDAI) and divided into 2 categories based on cutoffs recommended by the American College of Rheumatology: remission (CDAI<2.8, n=14), and active disease (CDAI≥2.8, n=45). One-tailed Wilcoxon rank sum tests were used to evaluate methylation differences between the two patient categories for candidate CpG sites previously found to be differentially methylated in fibroblast-like synoviocytes derived from RA patients compared to osteoarthritis patients or normal controls.

Results:  Of the 13,938 candidate loci, 1 CpG (cg05439368, upstream of TRIM69) was significantly hypermethylated and 1 CpG (cg07135032, in LMX1A) was significantly hypomethylated in CD4+ memory T cells (FDR q<0.05). No other CpG candidates achieved significance in the other cell types. CpGs within 1500 bp of TRIM69 were subsequently evaluated, and a block of 6 CpGs (including cg05439368) in the promoter region of TRIM69 was hypermethylated (p<0.05) in both the CD4+ memory and CD4+ naïve T cell subsets, suggesting that dysregulation of TRIM69 expression in CD4+ T cells may be associated with RA disease activity. TRIM69 has been reported to directly interact with a number of toll-like receptors (TLRs), a family of proteins involved in the innate immune response to microbial agents.

Conclusion:  Our results identify a potential biological mechanism underlying disease activity in RA cases. This study is the first to report methylation differences associated with RA CDAI scores.

Disclosure: A. Mok, None; B. Rhead, None; C. Holingue, None; X. Shao, None; D. Quach, None; H. L. Quach, None; E. Sinclair, None; J. D. Graf, None; T. M. Link, None; R. Harrison, None; V. Chernitskiy, None; W. Wang, None; G. S. Firestein, None; L. F. Barcellos, None; L. A. Criswell, None.

To cite this abstract in AMA style:

Mok A, Rhead B, Holingue C, Shao X, Quach D, Quach HL, Sinclair E, Graf JD, Link TM, Harrison R, Chernitskiy V, Wang W, Firestein GS, Barcellos LF, Criswell LA. DNA Methylation Profiling of Rheumatoid Arthritis Peripheral Blood Identifies Hypermethylation of TRIM69 Promoter Region in CD4+ T Cells Associated with Disease Activity [abstract]. Arthritis Rheumatol. 2015; 67 (suppl 10). https://acrabstracts.org/abstract/dna-methylation-profiling-of-rheumatoid-arthritis-peripheral-blood-identifies-hypermethylation-of-trim69-promoter-region-in-cd4-t-cells-associated-with-disease-activity/. Accessed .

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