ACR Meeting Abstracts

ACR Meeting Abstracts

Abstract Number: 1787

Innate Immunity, Arterial Inflammation and Vascular Stiffness in Patients with Systemic Lupus Erythematosus

Monica Purmalek1, Simantini Sakhardande1, Yenealem Temesgen-Oyelakin2, Alice Fike3, Taufiq Salahuddin4, Balaji Natarajan4, Zerai Manna2, Elizabeth Joyal2, Sarfaraz Hasni2, Nehal N. Mehta4 and Mariana J. 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, 3Office of the Clinical Director, National Institute of Arthritis and Musculoskeletal and Skin Diseases, National Institutes of Health, Bethesda, MD, 4NHLBI, National Institutes of Health, Bethesda, MD

Meeting: 2015 ACR/ARHP Annual Meeting

Date of first publication: September 29, 2015

Keywords: , , ,

Session Information

Date: Monday, November 9, 2015

Title: Systemic Lupus Erythematosus - Clinical Aspects and Treatment Poster Session II

Session Type: ACR Poster Session B

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

Background/Purpose: Patients with systemic lupus erythematosus (SLE) show a striking increase in risk of atherosclerotic cardiovascular disease (CVD) not explained by Framingham risk, compared to age and gender matched controls. Immune dysregulation and innate immune responses associated to aberrant neutrophils (low density granulocytes, LDGs) and neutrophil extracellular traps (NETs) may play key roles in conferring enhanced CV risk, driving vascular damage and, potentially, atherosclerosis. Whether neutrophils are associated to and predict vascular inflammation and eventually clinical vascular events remains to be determined. 

Methods: SLE patients fulfilling ACR classification criteria were compared to age and gender-matched controls. Clinical and demographic characteristics were recorded at each visit. Individuals underwent assessment of a) vascular function of various arterial territories (peripheral arterial tonometry of the microvasculature (Endopat) and arterial compliance by cardio-ankle vascular index (CAVI)); b) aortic inflammation by FDG-PET/CT; c) anatomical assessment of plaque by coronary CT angiogram. Circulating LDGs were quantified by flow cytometry and NET products in plasma were quantified by ELISA. 

Results:

Lupus (n=20) and healthy controls (n=15) did not differ in age, gender, ethnicity, tobacco use, Framingham score, or insulin resistance. Median disease duration was 20.5 years (IQR 9.3-54 years) and SLEDAI was 2+4.8. Arterial stiffness, assessed by CAVI and by Endopat augmentation index (AI), was increased in SLE  (CAVI: 7.24[5.6-9.3]) vs. controls (6.53[5.1-8.3]; p = 0.03; AI: 25.7[0.05-78.9]) vs. controls (6.81[-17.4-55.4], p = 0.003). SLE patients displayed enhanced arterial inflammation by FDG-PET/CT (target:background ratio (TBR; SLE 1.67(1.4-2.3) vs. controls 1.52( 1.4-1.7), p=0.05). Differences in control and SLE persisted in multivariate regression analysis adjusting for age and gender (TBR and Endopat), and Framingham risk score and BMI (CAVI and Endopat).Use of antimalarials or steroids was negatively associated with arterial stiffness (r=-0.44, p=0.05 and r=-0.51, p=0.02, respectively). LDGs, and plasma NET products were elevated in SLE and associated with enhanced arterial inflammation (TBR) and noncalcified plaque burden

Conclusion: Individuals with SLE demonstrate increased arterial stiffness and prominent arterial inflammation suggestive of enhanced risk for unstable plaque. Dysregulation in neutrophil function and NETosis occurs in vivo in SLE in association with arterial inflammation and vascular dysfunction. These observations indicate that neutrophils may be important drivers of vascular damage in SLE.

Disclosure: M. Purmalek, None; S. Sakhardande, None; Y. Temesgen-Oyelakin, None; A. Fike, None; T. Salahuddin, None; B. Natarajan, None; Z. Manna, None; E. Joyal, None; S. Hasni, None; N. N. Mehta, None; M. J. Kaplan, None.

To cite this abstract in AMA style:

Purmalek M, Sakhardande S, Temesgen-Oyelakin Y, Fike A, Salahuddin T, Natarajan B, Manna Z, Joyal E, Hasni S, Mehta NN, Kaplan MJ. Innate Immunity, Arterial Inflammation and Vascular Stiffness in Patients with Systemic Lupus Erythematosus [abstract]. Arthritis Rheumatol. 2015; 67 (suppl 10). https://acrabstracts.org/abstract/innate-immunity-arterial-inflammation-and-vascular-stiffness-in-patients-with-systemic-lupus-erythematosus/. Accessed .

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