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Abstract Number: 300

The DNA-Binding Protein ARID3a Is Associated with Interferon Alpha Production in Lupus Patient Plasmacytoid Dendritic Cells and Neutrophils

Michelle Ratliff1, Joshua Garton1,2, Indra Adrianto3, Ambra Pastori4, Courtney Montgomery5, Patrick Gaffney4, Judith A. James3,6 and Carol Webb1,7,8, 1Medicine, University of Oklahoma Health Sciences Center, Oklahoma City, OK, 2Chemistry, University of Oklahoma, Oklahoma City, OK, 3Arthritis and Clinical Immunology Program, Oklahoma Medical Research Foundation, Oklahoma City, OK, 4Arthritis and Clinical Immunology, Oklahoma Medical Research Foundation, Oklahoma City, OK, 5Arthritis & Clinical Immunology, Oklahoma Medical Research Foundation, Oklahoma City, OK, 6Department of Pathology, University of Oklahoma Health Sciences Center, Oklahoma City, OK, 7Cell Biology, University of Oklahoma Health Sciences Center, Oklahoma City, OK, 8Microbiology and Immunology, University of Oklahoma Health Sciences Center, Oklahoma City, OK

Meeting: 2017 ACR/ARHP Annual Meeting

Date of first publication: September 18, 2017

Keywords: interferons and transcription factor, Lupus

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Session Information

Date: Sunday, November 5, 2017

Title: Innate Immunity and Rheumatic Disease Poster I

Session Type: ACR Poster Session A

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

Background/Purpose: We previously demonstrated over-expression of the DNA-binding protein ARID3a in peripheral blood B lymphocytes from patients with systemic lupus erythematosus (SLE) compared to healthy controls. In addition, we found that ARID3a is induced in healthy control blood cells in response to toll receptor signaling, and specifically to CpG stimuli. Furthermore, ARID3a expression was associated with interferon alpha production in a subset of B lymphocytes from both CpG-stimulated healthy controls and SLE patients. Therefore we hypothesized that ARID3a might also be associated with interferon alpha production in other cell types that secrete interferons.

Methods: De-identified peripheral blood samples were obtained via our IRB approved protocol from SLE patients (classified via ACR criteria) and healthy age-matched control participants of the Oklahoma Rheumatic Diseases Core Center. Peripheral blood mononuclear cells were isolated over ficoll gradients and either subjected directly to immunofluorescence staining and flow cytometry analyses, or they were first subjected to magnetic bead enrichment for neutrophils or plasmacytoid dendritic cells (pDCs). Purified pDCs and neutrophils were subjected to RNA-seq and were evaluated for gene expression patterns in relation to ARID3a levels.

Results: Linear regression analyses demonstrated strong associations between ARID3a expression and interferon production in pDCs and neutrophils in SLE patients. In addition, ARID3a expression in those cell types was associated with increased SLE disease activity indices. Surprisingly, interferon subtypes were heterogeneously transcribed in neutrophils and pDCs. Gene expression data show increased interferon-associated transcripts in patients with increased ARID3a protein expression.

Conclusion: Our data indicate co-expression of ARID3a and interferon in SLE patient blood cells may be linked to interferon signatures observed in SLE.


Disclosure: M. Ratliff, None; J. Garton, None; I. Adrianto, None; A. Pastori, None; C. Montgomery, None; P. Gaffney, None; J. A. James, None; C. Webb, None.

To cite this abstract in AMA style:

Ratliff M, Garton J, Adrianto I, Pastori A, Montgomery C, Gaffney P, James JA, Webb C. The DNA-Binding Protein ARID3a Is Associated with Interferon Alpha Production in Lupus Patient Plasmacytoid Dendritic Cells and Neutrophils [abstract]. Arthritis Rheumatol. 2017; 69 (suppl 10). https://acrabstracts.org/abstract/the-dna-binding-protein-arid3a-is-associated-with-interferon-alpha-production-in-lupus-patient-plasmacytoid-dendritic-cells-and-neutrophils/. Accessed .
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