Interleukin-17/Interleukin-21 and Interferon-γ producing T cells specific for β2 Glycoprotein I in atherosclerosis inflammation of systemic lupus erythematosus patients with antiphospholipid syndrome

Marisa Benagiano, Maria Orietta Borghi, Jacopo Romagnoli, Michael Mahler, Chiara Della Bella, Alessia Grassi, Nagaja Capitani, Giacomo Emmi, Arianna Troilo, Elena Silvestri, Lorenzo Emmi, Heba Alnwaisri, Jacopo Bitetti, Simona Tapinassi, Domenico Prisco, Cosima Tatiana Baldari, Pier Luigi Meroni, Mario Milco D'Elios

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Abstract

Systemic lupus erythematosus is frequently associated with antiphospholipid syndrome. Patients with lupus-antiphospholipid syndrome are characterized by recurrent arterial/venous thrombosis, miscarriages, and persistent presence of autoantibodies against phospholipid-binding proteins, such as β2-Glycoprotein I. We investigated the cytokine production induced by β2-Glycoprotein I in activated T cells that infiltrate in vivo atherosclerotic lesions of lupus-antiphospholipid syndrome patients. We examined the helper function of β2-Glycoprotein I-specific T cells for tissue factor production, as well as their cytolytic potential and their helper function for antibody production. Lupus-antiphospholipid syndrome patients harbor in vivo activated CD4+ T cells that recognize β2-Glycoprotein I in atherosclerotic lesions. β2-Glycoprotein I induces T-cell proliferation and expression of both Interleukin-17/Interleukin-21 and Interferon-γ in plaque-derived T-cell clones. β2-Glycoprotein I-specific T cells display strong help for monocyte tissue factor production, and promote antibody production in autologous B cells. Moreover, plaque-derived β2-Glycoprotein I-specific CD4+ T lymphocytes express both perforin-mediated and Fas/FasLigand-mediated-cytotoxicity. Altogether, our results indicate that β2-Glycoprotein I is able to elicit a local Interleukin-17/Interleukin-21 and Interferon-γ inflammation in lupus-antiphospholipid syndrome patients that might lead, if unabated, to plaque instability and subsequent arterial thrombosis, suggesting that the T helper 17/T helper 1 pathway may represent a novel target for the prevention and treatment of the disease.

Original languageEnglish
Pages (from-to)2519-2527
Number of pages9
JournalHaematologica
Volume104
Issue number12
DOIs
Publication statusPublished - Dec 2019

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Benagiano, M., Borghi, M. O., Romagnoli, J., Mahler, M., Bella, C. D., Grassi, A., Capitani, N., Emmi, G., Troilo, A., Silvestri, E., Emmi, L., Alnwaisri, H., Bitetti, J., Tapinassi, S., Prisco, D., Baldari, C. T., Meroni, P. L., & D'Elios, M. M. (2019). Interleukin-17/Interleukin-21 and Interferon-γ producing T cells specific for β2 Glycoprotein I in atherosclerosis inflammation of systemic lupus erythematosus patients with antiphospholipid syndrome. Haematologica, 104(12), 2519-2527. https://doi.org/10.3324/haematol.2018.209536