ACR Meeting Abstracts

ACR Meeting Abstracts

Abstract Number: 2000

Immune Response Against  β2GPI Drives Th1 Inflammation in Atherosclerotic Plaques of Patients with Primary Antiphospholipid Syndrome

Pier Luigi Meroni1,2, Marisa Benagiano3, Maria Gerosa4, Jacopo Romagnoli5, Michael Mahler6, Maria Orietta Borghi7,8, Alessia Grassi9, Chiara Della Bella3, Giacomo Emmi3, Amedeo Amedei3,10, Elena Silvestri3, Lorenzo Emmi11, Domenico Prisco9,10 and Mario Milco D'Elios3,10, 1Clinical Sciences and Community Heath, Department of Clinical Sciences and Community Health, University of Milan, Milan, Italy, 2Laboratory of Immuno-rheumatology, Laboratory of Immuno-rheumatology, IRCCS Istituto Auxologico Italiano, Cusano Milanino, Italy, 3Department of Experimental and Clinical Medicine, Department of Experimental and Clinical Medicine, University of Florence, Florence, Italy, 4Division of Rheumatology, Department of Clinical Sciences and Community Health, Ospedale Gaetano Pini, University of Milan, Milano, Italy, 5Department of Surgery, Department of Surgery, Catholic University of Rome, Rome, Italy, 6Inova Diagnostics, San Diego, CA, 7Department of Clinical Sciences and Community Health, Department of Clinical Sciences and Community Health, University of Milan, Milan, Italy, 8Laboratory of Immuno-rheumatology, IRCCS Istituto Auxologico Italiano, Milan, Italy, 9Department of Experimental and Clinical Medicine,, Department of Experimental and Clinical Medicine, University of Florence, Florence, Italy, 10Internal Interdisciplinary Medicine Center for Autoimmune Systemic Diseases, Lupus Clinic, Internal Interdisciplinary Medicine Center for Autoimmune Systemic Diseases, Lupus Clinic, AOU Careggi, Florence, Italy, 11Internal Interdisciplinary Medicine Center for Autoimmune Systemic Diseases, Lupus Clinic,, Internal Interdisciplinary Medicine Center for Autoimmune Systemic Diseases, Lupus Clinic, AOU Careggi, Florence, Italy

Meeting: 2015 ACR/ARHP Annual Meeting

Date of first publication: September 29, 2015

Keywords: ,

Session Information

Date: Monday, November 9, 2015

Title: Antiphospholipid Syndrome: Recent findings

Session Type: ACR Concurrent Abstract Session

Session Time: 2:30PM-4:00PM

Background/Purpose:

Antiphospholipid syndrome (APS) is characterized by the presence of arterial and venous thrombosis, and by recurrent abortions, in patients with persistent presence of autoantibodies against phospholipid-binding proteins (aPL), such as β2-Glycoprotein I (β2GPI). Arterial thrombosis has been also related to accelerated atherosclerosis in experimental models, however  contrasting findings have been reported in clinical studies of patients with primary APS regarding an increased number of plaques or an abnormal arterial wall thickness. In spite of that, aPL predicts adverse arterial outcomes (Hollan et al Autoimmun Rev 12:1004;2013). Aim of the study was to investigate the role of the anti-β2GPI immune response in atherosclerotic lesions.

Methods:

We investigated the cytokine production induced by β2GPI, and its domains (DI, DII, DIII, DIV, DV) in activated T cells that infiltrate in vivo atherosclerotic lesions of patients with primary APS atherothrombosis. We also examined the helper function of β2GPI-specific T cells for monocyte matrix metalloproteinase (MMP)-9 and tissue factor (TF) production, as well as their cytolytic potential and their helper function for antibody production. 

Results:

We report that APS patients with atherothrombosis harbor in vivo activated CD4+ T cells that recognize β2GPI in atherothrombotic lesions. We characterized the submolecular specificity of  plaque infiltrating T cells and found that the majority of them recognize their epitopes within the DI domain. β2GPI and its domains induce T cell proliferation and expression of IFN-g in plaque-derived T cell clones. β2GPI-specific T cells display helper function for monocyte MMP-9 and TF production, and promote antibody production in autologous B cells. Moreover, plaque-derived β2GPI-specific CD4+ T lymphocytes express both perforin-mediated and Fas-FasLigand mediated cytotoxicity. 

Conclusion:

β2GPI, and especially DI domain, drive a local Th1 inflammatory response, with subsequent plaque instability which eventually favors atherothrombosis. This finding may explain the association between aPL and arterial thrombosis in spite of the lack of the evidence for surrogate markers of atherosclerosis – such as number of plaques and increased arterial wall thickness – in primary APS patients with high prevalence of arterial events.

Disclosure: P. L. Meroni, None; M. Benagiano, None; M. Gerosa, None; J. Romagnoli, None; M. Mahler, None; M. O. Borghi, None; A. Grassi, None; C. Della Bella, None; G. Emmi, None; A. Amedei, None; E. Silvestri, None; L. Emmi, None; D. Prisco, None; M. M. D'Elios, None.

To cite this abstract in AMA style:

Meroni PL, Benagiano M, Gerosa M, Romagnoli J, Mahler M, Borghi MO, Grassi A, Della Bella C, Emmi G, Amedei A, Silvestri E, Emmi L, Prisco D, D'Elios MM. Immune Response Against  β2GPI Drives Th1 Inflammation in Atherosclerotic Plaques of Patients with Primary Antiphospholipid Syndrome [abstract]. Arthritis Rheumatol. 2015; 67 (suppl 10). https://acrabstracts.org/abstract/immune-response-against-a-i%c2%b22gpi-drives-th1-inflammation-in-atherosclerotic-plaques-of-patients-with-primary-antiphospholipid-syndrome/. Accessed .

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