ACR Meeting Abstracts

ACR Meeting Abstracts

Abstract Number: 3102

Neutrophil Subsets, Arterial Inflammation, and Vascular Stiffness in Patients with Systemic Lupus Erythematosus

Monica Purmalek1, Simantini Sakhardande1, Yenealem Temesgen-Oyelakin2, Aditya Joshi3, Joseph Lerman4, Michael Davis3, Alice Fike5, Amit Dey6, Taufiq Salahuddin7, Balaji Natarajan3, Martin P. Playford7, Heather Teague3, Zerai G. Manna5, Marcus Chen3, Sarfaraz Hasni5, Nehal N. Mehta7 and Mariana Kaplan1, 1Systemic Autoimmunity Branch, National Institute of Arthritis and Musculoskeletal and Skin Diseases, National Institutes of Health, Bethesda, MD, 2National Institute of Arthritis and Musculoskeletal and Skin Diseases,, National Institutes of Health, Bethesda, MD, 3NIH, Bethesda, MD, 4Clinical Center, NIH, Bethesda, MD, 5National Institute of Arthritis and Musculoskeletal and Skin Diseases, National Institutes of Health, Bethesda, MD, 6National Institutes of Health, Bethesda, MD, 7NHLBI, National Institutes of Health, Bethesda, MD

Meeting: 2016 ACR/ARHP Annual Meeting

Date of first publication: September 28, 2016

Keywords: , ,

Session Information

Date: Tuesday, November 15, 2016

Title: Systemic Lupus Erythematosus – Clinical Aspects and Treatment IV: Biomarkers

Session Type: ACR Concurrent Abstract Session

Session Time: 4:30PM-6:00PM

Background/Purpose: Patients with systemic lupus erythematosus (SLE) show a striking increase in risk of atherosclerotic cardiovascular disease (CVD) not explained by Framingham risk, when compared to age and gender matched controls. Immune dysregulation and innate immune responses associated to aberrant neutrophils (low density granulocytes, LDGs) may play a key role in conferring enhanced CV risk, driving vascular damage, oxidizing HDL and altering its function. Whether proinflammatory neutrophils are associated to and predict vascular inflammation, endothelial dysfunction, and eventually, clinical vascular events remains to be determined.

Methods: In this cross-sectional study, SLE patients fulfilling ACR classification criteria were compared to age and gender-matched controls. Clinical and demographic characteristics, Framingham Risk score, metabolic parameters, and lupus medications were recorded at each visit. Individuals underwent assessment of a) vascular function of various arterial territories: peripheral arterial tonometry of the microvasculature (Endopat), arterial stiffness by cardio-ankle vascular index (CAVI) and by Sphygmocor; b) aortic inflammation by FDG-PET/CT; and c) anatomical assessment of plaque by coronary CT angiogram. Circulating LDGs were quantified by flow cytometry. Cholesterol efflux capacity was quantified in radioactively-labeled cell lines upon exposure to control or lupus HDL.

Results: Lupus (n=54) and healthy controls (n=32) did not differ in gender, race, ethnicity or Framingham risk score. Mean disease duration was 16 ± 12 years and SLEDAI was 3.5 + 2.9. Arterial stiffness assessed by CAVI was increased in SLE (CAVI: 7.3[6.5-8.0]) vs. controls (6.3[5.9-7.4]; p = 0.004), and by Endopat augmentation index (AI75: 14.4 ± 18.7) vs. controls (5.5 ± 20.7, p = 0.022). Additionally, SLE patients displayed enhanced aortic inflammation by FDG-PET/CT (TBR: 1.63 [1.5-1.8]) vs. controls (1.56 [1.5-1.7], p=0.010). Differences between control and SLE persisted in multivariate regression analysis adjusting for Framingham Risk. HDL efflux was negatively associated with noncalcified plaque burden in SLE (b=-0.30, p=0.002), while LDGs were positively associated with noncalcified plaque burden (b=0.37, p<0.001), both persisting in multivariate regression analysis adjusting for Framingham Risk + body mass index or insulin resistance. In addition, number of lupus LDGs positively associated with damage (SLICC score (b=0.31, p=0.031)), CRP (b=0.46, p=0.001), and arterial stiffness (b=0.44, p=0.012).

Conclusion: Individuals with SLE demonstrate increased arterial stiffness and prominent arterial inflammation suggestive of widespread damage across both micro- and macro-vascular territories. These results support the hypothesis that aberrant neutrophil subsets significantly contribute to vascular damage and unstable plaque development in SLE. Results also support previous observations that neutrophils, through enhanced neutrophil extracellular trap formation, may disrupt HDL function and further promote atherogenesis.

Disclosure: M. Purmalek, None; S. Sakhardande, None; Y. Temesgen-Oyelakin, None; A. Joshi, None; J. Lerman, None; M. Davis, None; A. Fike, None; A. Dey, None; T. Salahuddin, None; B. Natarajan, None; M. P. Playford, None; H. Teague, None; Z. G. Manna, None; M. Chen, None; S. Hasni, None; N. N. Mehta, None; M. Kaplan, None.

To cite this abstract in AMA style:

Purmalek M, Sakhardande S, Temesgen-Oyelakin Y, Joshi A, Lerman J, Davis M, Fike A, Dey A, Salahuddin T, Natarajan B, Playford MP, Teague H, Manna ZG, Chen M, Hasni S, Mehta NN, Kaplan M. Neutrophil Subsets, Arterial Inflammation, and Vascular Stiffness in Patients with Systemic Lupus Erythematosus [abstract]. Arthritis Rheumatol. 2016; 68 (suppl 10). https://acrabstracts.org/abstract/neutrophil-subsets-arterial-inflammation-and-vascular-stiffness-in-patients-with-systemic-lupus-erythematosus/. Accessed .

« Back to 2016 ACR/ARHP Annual Meeting

ACR Meeting Abstracts - https://acrabstracts.org/abstract/neutrophil-subsets-arterial-inflammation-and-vascular-stiffness-in-patients-with-systemic-lupus-erythematosus/