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 the 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.

Interleukin-17/Interleukin-21 and Interferon-g producing T cells specific for β2 Glycoprotein I in atherosclerosis inflammation of systemic lupus erythematosus patients with antiphospholipid syndrome / Benagiano, Marisa; Borghi, Maria Orietta; Romagnoli, Jacopo; Mahler, Michael; Della Bella, Chiara; Grassi, Alessia; Capitani, Nagaja; Emmi, Giacomo; Troilo, Arianna; Silvestri, Elena; Emmi, Lorenzo; Alnwaisri, Heba; Bitetti, Jacopo; Tapinassi, Simona; Prisco, Domenico; Baldari, Cosima Tatiana; Meroni, Pier Luigi; D'Elios, Mario Milco. - In: HAEMATOLOGICA. - ISSN 1592-8721. - ELETTRONICO. - (2019), pp. 1-48. [10.3324/haematol.2018.209536]

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

Benagiano, Marisa;Della Bella, Chiara;Grassi, Alessia;Capitani, Nagaja;Emmi, Giacomo;Troilo, Arianna;Silvestri, Elena;Emmi, Lorenzo;Alnwaisri, Heba;Bitetti, Jacopo;Tapinassi, Simona;Prisco, Domenico;D'Elios, Mario Milco
2019

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 the 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.
2019
1
48
Benagiano, Marisa; Borghi, Maria Orietta; Romagnoli, Jacopo; Mahler, Michael; Della Bella, Chiara; Grassi, Alessia; Capitani, Nagaja; Emmi, Giacomo; Troilo, Arianna; Silvestri, Elena; Emmi, Lorenzo; Alnwaisri, Heba; Bitetti, Jacopo; Tapinassi, Simona; Prisco, Domenico; Baldari, Cosima Tatiana; Meroni, Pier Luigi; D'Elios, Mario Milco
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Utilizza questo identificatore per citare o creare un link a questa risorsa: https://hdl.handle.net/2158/1178407
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