ACR Meeting Abstracts

ACR Meeting Abstracts

Abstract Number: 2654

Treatment-Associated DNA Methylation Patterns in Systemic Lupus Erythematosus

Juliana Imgenberg-Kreuz1,2, Jonas Carlsson Almlöf1, Dag Leonard3, Gunnel Nordmark2, Maija-Leena Eloranta3, Leonid Padyukov4, Iva Gunnarsson4, Elisabet Svenungsson4, Christopher Sjöwall5, Lars Rönnblom2, Ann-Christine Syvänen1 and Johanna K Sandling1,2, 1Department of Medical Sciences, Molecular Medicine and Science for Life Laboratory, Uppsala University, Uppsala, Sweden, Uppsala, Sweden, 2Department of Medical Sciences, Section of Rheumatology, Uppsala University, Uppsala, Sweden, Uppsala, Sweden, 3Rheumatology and Science for Life Laboratory, Department of Medical Sciences, Uppsala University, Sweden, Uppsala, Sweden, 4Department of Medicine Solna, Rheumatology Unit, Karolinska Institutet, Karolinska University Hospital, Stockholm, Sweden, Stockholm, Sweden, 5Department of Clinical and Experimental Medicine, Rheumatology/AIR, Linköping University, Linköping, Sweden, Linköping, Sweden

Meeting: 2017 ACR/ARHP Annual Meeting

Date of first publication: September 18, 2017

Keywords: , , ,

Session Information

Date: Tuesday, November 7, 2017

Title: Systemic Lupus Erythematosus – Human Etiology and Pathogenesis Poster II

Session Type: ACR Poster Session C

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

Background/Purpose:

DNA methylation has emerged as an important contributing factor in the pathogenesis of systemic lupus erythematosus (SLE). SLE typically requires continuous treatment to control the disease, but the effect of different treatments on DNA methylation is still elusive. Therefore the aim of this study was to investigate the association between methylation levels in SLE patients and the most commonly prescribed medications in SLE.

Methods:

Whole blood samples were obtained from 347 SLE patients in a discovery cohort and from 201 SLE patients in a replication cohort, all fulfilling at least four ACR criteria for SLE. Clinical data regarding medication were collected at the time of blood sampling, and treatment with glucocorticoids, chloroquines, azathioprine, mycophenolate mofetil and methotrexate were included in the analysis. DNA methylation profiles were generated on the Illumina HumanMethylation 450k BeadChip array, interrogating 485,000 CpG sites across the genome. The association model included differential cell count estimations, age and sex as covariates. Differential methylated CpG sites (DMCs) were called in the discovery phase if they had a p <1.3×10-7 and an average difference in methylation-beta between treated and untreated cases of >0.05. For the replication phase significance was determined as p<6.8×10-6 and the same direction of effect as observed in the discovery phase.

Results:

We identified and replicated treatment-associated DMCs at a total of 5,177 CpG sites. The vast majority of medication DMCs (n=5,046) were observed by comparing SLE patients that received glucocorticoid treatment at time of blood sampling (n=347) to those who did not (n=201). Glucocorticoid treatment was typically associated with decreased methylation, where the strongest effect was observed at the FK506 binding protein 5 (FKBP5) involved in immune regulation. The top DMCs with increased methylation in glucocorticoid treated patients were located in RUNX3, TMEM63A, ZFP36L1 and LTA. In addition, we identified 130 DMCs for azathioprine and one DMC for mycophenolate mofetil treatment, all of these with decreased methylation levels in the treated patients. We were not able to replicate any DMCs associated with methotrexate or chloroquine treatment.

Conclusion:

Our results indicate a role for treatment-associated DNA methylation patterns in SLE, although the possible impact of clinical manifestations and disease activity on methylation levels must be taken into account. Changes in methylation may reflect exposure to treatment and contribute to treatment response and adverse effects. Additional studies including analyses of longitudinal medication data will further elucidate the potential functional impact of treatment-associated changes in DNA methylation in patients with SLE.

Disclosure: J. Imgenberg-Kreuz, None; J. Carlsson Almlöf, None; D. Leonard, None; G. Nordmark, None; M. L. Eloranta, None; L. Padyukov, None; I. Gunnarsson, None; E. Svenungsson, None; C. Sjöwall, None; L. Rönnblom, None; A. C. Syvänen, None; J. K. Sandling, None.

To cite this abstract in AMA style:

Imgenberg-Kreuz J, Carlsson Almlöf J, Leonard D, Nordmark G, Eloranta ML, Padyukov L, Gunnarsson I, Svenungsson E, Sjöwall C, Rönnblom L, Syvänen AC, Sandling JK. Treatment-Associated DNA Methylation Patterns in Systemic Lupus Erythematosus [abstract]. Arthritis Rheumatol. 2017; 69 (suppl 10). https://acrabstracts.org/abstract/treatment-associated-dna-methylation-patterns-in-systemic-lupus-erythematosus/. Accessed .

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