ACR Meeting Abstracts

ACR Meeting Abstracts

Abstract Number: 0867

A Proteomic/Transcriptomic Analysis Associates with Subclinical Vascular Disease in Systemic Lupus Erythematosus

Christopher Oliveira1, Yenealem Temesgen-Oyelakin2, Mohammad Naqi3, Nidhi Patel2, Philip Parel2, Massimo Gadina4, Stefania Dell'Orso2, Stephen Brooks2, Sarthak Gupta5, Nehal Mehta6, Sarfaraz Hasni3 and Mariana Kaplan3, 1National Institutes of Health (NIH), Vienna, VA, 2National Institutes of Health (NIH), Bethesda, MD, 3National Institutes of Health, Bethesda, MD, 4National Institute of Arthritis and Musculoskeletal and Skin Diseases, Bethesda, MD, 5National Institutes of Arthritis and Musculoskeletal and Skin Diseases (NIAMS), National Institutes of Health (NIH), Bethesda, MD, 6NHLBI/National Institutes of Health, Bethesda, MD

Meeting: ACR Convergence 2021

Keywords: , , ,

Session Information

Date: Sunday, November 7, 2021

Title: SLE – Diagnosis, Manifestations, & Outcomes Poster II: Manifestations (0855–0896)

Session Type: Poster Session B

Session Time: 8:30AM-10:30AM

Background/Purpose: Systemic lupus erythematosus (SLE) is associated with enhanced cardiovascular (CV) risk linked to both traditional Framingham risk factors and lupus-specific immune dysregulation. Characterizing an immunological signature at the transcriptional and protein level that associates with subclinical vascular disease and predicts atherosclerosis progression has been challenging.

Methods: SLE patients and matched healthy controls underwent assessments of vascular stiffness (cardio-ankle vascular index (CAVI)), vascular inflammation by FDG-PET CT, and coronary artery plaque by coronary computed tomography angiography (CCTA). Whole blood RNA sequencing was performed in samples from a subset of those patients including 10 controls and 20 SLE patients. In a larger subset of these patients including 24 controls and 64 SLE patients, measurement of several inflammatory biomarkers using the Olink platform was performed. The findings were correlated with clinical and vascular assessments.

Results: In initial pathway analyses, transcriptional regulation of genes related to cell cycle processes was observed in SLE patients with more severe vascular disease compared to SLE patients with milder vascular phenotypes. Additionally, upregulation of pathways related to cytokine-mediated signaling and response to interferon-gamma was also noted between these groups but was driven by changes in expression of only a small selection of genes. Within SLE patients, proteomic analyses revealed fourteen immunologic and inflammatory-linked proteins (CCL11, IL18R1, IL20RA, IL6, IL7, LIF, CDCP1, IL22RA, LAP TGF-β1, LIFR, MCP3, TNFSF14, TRANCE, X4EBP1) which correlate with more than one cardiovascular readout. Of specific interest, these analyses reveal four proteins that correlate significantly with non-calcified plaque burden (IL6, LIFR, IL22RA1, IL4) and thirteen different proteins which correlate with dense calcified plaque burden (CCL11, IL1α, IL20, IL20RA, IL2RB, IL2, IL5, IL7, LIF, MCP3, MCP4, MMP1, TNFSF14),). Of note, decreased leukemia inhibitory factor receptor (LIFR) and increased IL6 were associated with both increased vascular inflammation, total plaque burden and non-calcified plaque burden in SLE patients.

Conclusion: Several inflammatory serum markers associate with enhanced vascular damage in SLE. Of note, dysregulation of the LIF/IL6 axis, described to be involved in regulation of the fate of T-cells, may represent both a marker of increased atherosclerotic plaque burden risk and a mechanism by which plaque burden worsens in SLE patients, potentially driven by changes in lymphocyte composition. Thus, further investigation of the influence of the LIF/IL6 axis and T-cell subsets is warranted in understanding the pathogenesis of cardiovascular disease in SLE. Additionally, given the transcriptomic data, investigation of the role of cell cycle processes in cardiovascular risk in SLE may also prove valuable.

Disclosures: C. Oliveira, None; Y. Temesgen-Oyelakin, None; M. Naqi, None; N. Patel, None; P. Parel, None; M. Gadina, None; S. Dell'Orso, None; S. Brooks, None; S. Gupta, None; N. Mehta, NIH, 5, Astra Zeneca, 5, Celgene/Amgen, 5, Novartis, 5, Abbvie, 5, Abcentra, 1, 5, Janssen, 5, NPF, 1, 5; S. Hasni, None; M. Kaplan, None.

To cite this abstract in AMA style:

Oliveira C, Temesgen-Oyelakin Y, Naqi M, Patel N, Parel P, Gadina M, Dell'Orso S, Brooks S, Gupta S, Mehta N, Hasni S, Kaplan M. A Proteomic/Transcriptomic Analysis Associates with Subclinical Vascular Disease in Systemic Lupus Erythematosus [abstract]. Arthritis Rheumatol. 2021; 73 (suppl 9). https://acrabstracts.org/abstract/a-proteomic-transcriptomic-analysis-associates-with-subclinical-vascular-disease-in-systemic-lupus-erythematosus/. Accessed .

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ACR Meeting Abstracts - https://acrabstracts.org/abstract/a-proteomic-transcriptomic-analysis-associates-with-subclinical-vascular-disease-in-systemic-lupus-erythematosus/