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Abstract Number: 151

Differences in Chromatin Architecture Between Treatment-Naïve Pediatric and Adult Lupus Patients

Joyce Hui-Yuen1, Frank Jenkins 2, Kaiyu Jiang 3, Betty Diamond 2 and James Jarvis 4, 1Cohen Children's Medical Center, New Hyde Park, 2Northwell Health, Manhasset, 3University at Buffalo, Buffalo, 4University at Buffalo Jacobs School of Medicine, Buffalo

Meeting: 2020 Pediatric Rheumatology Symposium

Keywords: ATACseq, Epigenetics, Systemic lupus erythematosus (SLE)

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Session Information

The 2020 Pediatric Rheumatology Symposium, originally scheduled for April 29 – May 2, was postponed due to COVID-19; therefore, abstracts were not presented as scheduled.

Date: Thursday, April 30, 2020

Session Title: Poster Session 1

Session Type: ACR Abstract Session

Session Time: 6:00PM-7:00PM

Background/Purpose: Systemic lupus erythematosus (SLE) is possibly triggered by gene-environment interactions. We showed most of the SLE haplotypes contain epigenetic marks associated with enhancer function in immune cells, suggesting altered gene regulation. Data remain scarce on how epigenetic variance contributes to disease risk in pediatric SLE (pSLE). Here we sought to identify differences in chromatin architecture in B cells of treatment-naïve pSLE compared to healthy children (HC), and compared these differences to epigenetic data from B cells of treatment-naïve adult SLE (aSLE) patients.

Methods: We used the assay for transposase-accessible chromatin-sequencing (ATACseq) in 8 treatment-naïve pSLE patients and 5 HC to investigate whether regions of open chromatin unique to pSLE patients demonstrate enrichment for transcriptional regulators, using standard computational approaches and a false discovery rate of < 0.05. We used Limma to interrogate rppm normalized aSLE data from a public GEO set to compare our pSLE findings.

Results: The mean age of onset was 13.75 (range 7-17) years in pSLE, with mean SLEDAI of 12.8 (range 6-24). We identified 245 differentially accessible regions (DAR) around peaks unique to pSLE, of which over 50% appear to be more accessible in pSLE than HC, and 158 overlap known SLE genetic risk loci. Of the unique peaks, 46-60% are located more than 100kb from the nearest transcription start site (nTSS), implying many transcription factors may be acting on distal enhancers to regulate transcription. Variant calling within DAR found 3864 genes belonging to 129 different biologic processes (BP), most notably cellular activation in immune response, regulation of proliferation, and responses to external stimuli. Similar results were seen in aSLE: over 50% of peaks in aSLE are located distal to nTSS, and 3263 genes within DAR belong to 135 different BP, including cellular activation in immune response and complement activation.

Conclusion: We demonstrate an epigenetically-distinct profile in pSLE B cells when compared to HC, indicating pSLE B cells are predisposed for disease development. Pathways of significance analyses identified immunologic pathways important in the pro-inflammatory response in pSLE and aSLE patients. Thus, increased chromatin accessibility in genomic regions controlling activation of the inflammatory and immune responses suggest transcriptional dysregulation of key players in immune cell activation plays an important role in pathogenesis of SLE.


Disclosure: J. Hui-Yuen, None; F. Jenkins, None; K. Jiang, None; B. Diamond, None; J. Jarvis, None.

To cite this abstract in AMA style:

Hui-Yuen J, Jenkins F, Jiang K, Diamond B, Jarvis J. Differences in Chromatin Architecture Between Treatment-Naïve Pediatric and Adult Lupus Patients [abstract]. Arthritis Rheumatol. 2020; 72 (suppl 4). https://acrabstracts.org/abstract/differences-in-chromatin-architecture-between-treatment-naive-pediatric-and-adult-lupus-patients/. Accessed June 2, 2023.
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