Session Information
Date: Tuesday, November 10, 2015
Title: Systemic Lupus Erythematosus - Clinical Aspects and Treatment Poster Session III
Session Type: ACR Poster Session C
Session Time: 9:00AM-11:00AM
Background/Purpose:
Type I interferon (IFN) may affect endothelial progenitor cells leading to endothelial dysfunction in SLE. SLE patients have a type I IFN signature in platelets associated with cardiovascular disease (CVD). The objectives were to investigate if there is an association between type I IFN activation, endothelial dysfunction and platelet activation in SLE and if young SLE patients have increased arterial stiffness and impaired endothelial function.
Methods:
SLE patients n=148,(n=144 fulfilling≥ 4 ACR classification criteria for SLE, 87% women, mean age 49 years old) and 79 sex- and age matched healthy controls (HC) were tested. Endothelial dysfunction (ED) and Augmentation Index (AI) were measured by EndoPAT 2000 (Itamar Medical, Israel). Elevated AI indicates increased arterial stiffness and a low Reactive Hyperemia Index (RHI) value indicates ED. Surrogate markers for ED; sVCAM-1 and vWF were measured with ELISA. Type I IFN activity was measured by a serum IFN-reporter gene expression assay (s-IFN score), type I IFN signature was assessed in peripheral blood mononuclear cells (PBMCs) as PBMC- IFN and the type I IFN regulated protein G3BP was measured by ELISA.
Platelet activation was measured as levels of platelet C4d deposition (p-C4d dep), platelet- monocyte complex (p-mc compl) and platelet- granulocyte complex (p-gc compl), measured by flow cytometry.
Results:
A low RHI was seen in SLE patients with ongoing type I IFN activity compared to HC (OR 2.61 CI 95% 1.04-6.53 p= 0.04). No differences were seen when comparing all SLE patients with HC (OR 1.30 CI 95% 0.66-2.58 p=0.450).
ED (low RHI and/or high sVCAM-1) was seen in SLE patients with ongoing type I IFN activity measured as IFN score, G3BP and high PBMC-IFN signature.
High sVCAM-1, was seen in patients with a high value of s-IFN score (OR 6.12 CI 95% 2.21-16.93 p<0.001), a high G3BP level (OR 3.38 CI 95% 1.41-8.06 p=0.006) and high levels of PBMC- IFN (OR 7.89 CI 95% 2.87-21.7 p<0.0001). ED measured with a low RHI was seen in patients with high s-IFN score (OR 2.53 CI 95% 1.07-5.97 p=0.035) and high G3BP (OR 2.36 CI 95% 1.025-5.45 p=0.044)
Young SLE patients seemed to have increased arterial stiffness compared to HC, since AI was clearly increased (OR 2.95 CI 95% 1.24-7.02 p=0.015) in SLE patients 18-45 years of age.
High levels of p-C4d dep and p-mc compl were seen in SLE compared to HC (OR 13,5 CI 95% 4.07-45.1 p<0.000) and (OR 2.84 CI 95% 1.19-6.8 p=0.019), respectively, demonstrating more activated platelets in SLE. SLE patients with low RHI had increased levels of p-mc compl (OR 2.92 CI 95% 1.22-6.99 p=0.016). SLE patients with high sVCAM-1 had increased p-gc compl and p-C4d dep (OR 3.39 CI 95% 1.19-9.66 p=0.022) and (OR 3.33 CI 95% 1.58-7.03 p= 0.002), respectively showing more activated platelets in SLE patients with ED.
Conclusion:
Increased arterial stiffness was seen in young SLE patients, suggesting that early primary preventive treatment might be important already in younger patients.
SLE patients with activated type I IFN system have impaired endothelial function. This may act together with activated platelets due to injured endothelium, in the development of CVD in SLE.
To cite this abstract in AMA style:
Tydén H, Lood C, Gullstrand B, Jönsen A, Bengtsson AA. Endothelial Dysfunction in SLE-the Role of Platelets and Type I Interferon [abstract]. Arthritis Rheumatol. 2015; 67 (suppl 10). https://acrabstracts.org/abstract/endothelial-dysfunction-in-sle-the-role-of-platelets-and-type-i-interferon/. Accessed .« Back to 2015 ACR/ARHP Annual Meeting
ACR Meeting Abstracts - https://acrabstracts.org/abstract/endothelial-dysfunction-in-sle-the-role-of-platelets-and-type-i-interferon/