Session Type: ACR Poster Session C
Session Time: 9:00AM-11:00AM
Background/Purpose: In several autoimmune diseases, most notably in systemic lupus erythematosus (SLE), a type I interferon (IFN) signature has been described. This signature is thought to be related to the activation of plasmacytoid dendritic cells (pDCs) and their subsequent production of type I IFN. Whether a type I IFN signature is also present in patients with (primary) antiphospholipid syndrome ((P)APS) and its contribution to its pathophysiology is as of yet unknown. Therefore, we assessed the presence of a type I IFN signature in monocytes of SLE, SLE+APS and PAPS patients and determined the frequency of pDCs as key producers of type I IFN.
Methods: The expression of four type I IFN inducible genes Ly6E, IFITM1, IFI44L and Serping-1 was determined by RT-qPCR in monocytes isolated from peripheral blood of healthy controls (HC, n=24), patients with SLE (n=52), SLE+APS (n=30) and PAPS (n=24). Expression levels were used to calculate a type I IFN signature score. The frequency of pDCs was determined by flow cytometry by double positive staining for BDCA2 and BDCA4. The percentage of classical, intermediate and non-classical monocyte subsets was determined by CD14 and CD16 expression using flow cytometry on isolated monocytes.
Results: The mean (±95% confidence interval) type I IFN score was 1.91 (1.52 – 2.30, p<0.001) in SLE patients, 1.74 (1.27 – 2.20, p<0.001) in SLE+APS patients and 0.97 (0.41 – 1.54, p=0.03) in PAPS patients as compared with 0.00 (-0.36 – 0.36) in HC. SLE patients had a statistically significant higher type I IFN score as compared with PAPS patients (p=0.014). The median frequency (interquartile range) of pDCs in SLE, SLE+APS and PAPS was respectively 0.22% (0.15 – 0.38, p=0.005), 0.24% (0.20 – 0.30, p=0.003) and 0.18% (0.14 – 0.35, p=0.004) as compared with 0.40% (0.25 – 0.49) in HC. In patients with SLE, the type I IFN score correlated with disease activity. Although not related to a clinical or serological APS phenotype or the expression of tissue factor, the type I IFN score correlated with the proportion of monocytes subsets in APS patients.
Conclusion: We confirm the presence of a type I IFN signature in monocytes of SLE patients but show for the first time the presence of this in PAPS patients as well. In line what has been reported in SLE, pDCs frequencies are reduced in the circulation of PAPS patients as well. Altogether, these observations justify further research into the role of pDCs in the pathogenesis of PAPS aside to that in SLE.
To cite this abstract in AMA style:van den Hoogen LL, Fritsch-Stork RDE, Versnel MA, Derksen RHWM, van Roon JAG, Radstake TRDJ. A Type I Interferon Signature in Monocytes and Decreased Levels of Circulating Plasmacytoid Dendritic Cells in Patients with Primary Antiphospholipid Syndrome [abstract]. Arthritis Rheumatol. 2016; 68 (suppl 10). https://acrabstracts.org/abstract/a-type-i-interferon-signature-in-monocytes-and-decreased-levels-of-circulating-plasmacytoid-dendritic-cells-in-patients-with-primary-antiphospholipid-syndrome/. Accessed May 16, 2022.
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ACR Meeting Abstracts - https://acrabstracts.org/abstract/a-type-i-interferon-signature-in-monocytes-and-decreased-levels-of-circulating-plasmacytoid-dendritic-cells-in-patients-with-primary-antiphospholipid-syndrome/