ACR Meeting Abstracts

ACR Meeting Abstracts

Abstract Number: 802

Whole Transcriptome Profiling through RNA Sequencing Reveals Differentially Expressed Sense-Antisense Gene Pairs in Patients with Systemic Sclerosis

Tobias Messemaker1,2, Loubna Chadli3, Varshna Goelela3, Maaike Boonstra4, Annemarie Dorjee4, Stefan Andersen3, Harald Mikkers2, Tom WJ Huizinga4, Zhenghui Li5, Guoshuai Cai5, Michael Whitfield6, René Toes7, Jamil Aarbiou3, Jeroen De Groot3, Jeska K. de Vries-Bouwstra4 and Fina Kurreeman4, 1Department of Rheumagoloty, Leiden University Medical Center, Leiden, Netherlands, 2Department of Molecular cell Biology, Leiden University Medical Center, Leiden, Netherlands, 3Charles River Nederland B.V., Leiden, Netherlands, 4Department of Rheumatology, Leiden University Medical Center, Leiden, Netherlands, 5Department of Genetics, Geisel School of Medicine at Dartmouth, Hanover, NH, 6Department of Molecular and Systems Biology, Geisel School of Medicine at Dartmouth, Hanover, NH, 7Rheumatology, Leiden University Medical Center, Leiden, Netherlands

Meeting: 2016 ACR/ARHP Annual Meeting

Date of first publication: September 28, 2016

Keywords: ,

Session Information

Date: Sunday, November 13, 2016

Title: Systemic Sclerosis, Fibrosing Syndromes and Raynaud's – Pathogenesis, Animal Models and Genetics - Poster I

Session Type: ACR Poster Session A

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

Background/Purpose: Systemic sclerosis (SSc) is an autoimmune disease characterized by fibrosis of skin and multiple organs. Morbidity and mortality are high and pathogenesis is poorly understood. Previous global gene expression studies have shown skin gene profiles with fibrotic as well as inflammatory signatures. Available treatment options are mainly based on suppression of inflammation and are only partially effective. Understanding the basis of the development and progression of SSc is therefore important to lead to deeper understanding of the disease process and to investigate better treatment options. In the current study, we aimed to identify gene expression changes in coding and non-coding RNAs in skin tissue of SSc patients as compared to healthy individuals, with a specific focus on anti-sense RNAs.

Methods: Skin biopsy-derived RNA from fourteen SSc patients and six healthy individuals was sequenced using ion-torrent next generation sequencing technology. Both protein-coding and non-coding genes annotated in Gencode V7 (GRCh38, Ensemble 83) were analysed. Validation of differentially expressed genes was performed by reverse transcriptase qPCR, comparison with a public microarray RNA dataset and validation in an independent SSc skin RNA-sequencing dataset. We focussed on non-coding RNAs and more specifically the dysregulation of non-coding antisense RNAs and their sense-stranded counterpart genes.

Results: We found 619 genes that are consistently differentially expressed and overlapped with a previously published microarray-based study. More than 95% of genes showed the same directionality of expression. Overall we find an enrichment of induced genes in immunological, cell adhesion and keratin related processes. Further analyses of specific genesets revealed induced expression of 80% of the keratin genes and an induction of genes associated with interferon and alternatively activated macrophage gene signatures. Analysis of non-coding RNAs reveals 676 deregulated non-coding genes of which a majority are classified as antisense genes. Antisense genes have shown regulatory roles on gene expression of often sense-stranded genes and for 62 differentially expressed antisense genes a coding sense gene was identified. Interestingly, a significant proportion of these sense genes (26 out of 62) were also deregulated in patients suggesting a link within these sense-antisense gene pairs which might have a role in the underlying mechanisms contributing to the disease.

Conclusion: Our data highlight significant differences between anti-sense non-coding genes expressed in SSc tissue as compared to healthy individuals. To our knowledge, our data provide for the first time evidence for the role of anti-sense genes in the regulation of differential gene expression in SSc patient-derived tissue.

Disclosure: T. Messemaker, None; L. Chadli, None; V. Goelela, None; M. Boonstra, None; A. Dorjee, None; S. Andersen, None; H. Mikkers, None; T. W. Huizinga, None; Z. Li, None; G. Cai, None; M. Whitfield, None; R. Toes, None; J. Aarbiou, None; J. De Groot, None; J. K. de Vries-Bouwstra, None; F. Kurreeman, None.

To cite this abstract in AMA style:

Messemaker T, Chadli L, Goelela V, Boonstra M, Dorjee A, Andersen S, Mikkers H, Huizinga TW, Li Z, Cai G, Whitfield M, Toes R, Aarbiou J, De Groot J, de Vries-Bouwstra JK, Kurreeman F. Whole Transcriptome Profiling through RNA Sequencing Reveals Differentially Expressed Sense-Antisense Gene Pairs in Patients with Systemic Sclerosis [abstract]. Arthritis Rheumatol. 2016; 68 (suppl 10). https://acrabstracts.org/abstract/whole-transcriptome-profiling-through-rna-sequencing-reveals-differentially-expressed-sense-antisense-gene-pairs-in-patients-with-systemic-sclerosis/. Accessed .

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