TY - JOUR AU - Marisa Benagiano, AU - Maria Orietta Borghi, AU - Jacopo Romagnoli, AU - Michael Mahler, AU - Chiara Della Bella, AU - Alessia Grassi, AU - Nagaja Capitani, AU - Giacomo Emmi, AU - Arianna Troilo, AU - Elena Silvestri, AU - Lorenzo Emmi, AU - Heba Alnwaisri, AU - Jacopo Bitetti, AU - Simona Tapinassi, AU - Domenico Prisco, AU - Cosima Tatiana Baldari, AU - Pier Luigi Meroni, AU - Mario Milco D’Elios, PY - 2019/12/01 Y2 - 2024/03/29 TI - 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 JF - Haematologica JA - haematol VL - 104 IS - 12 SE - Articles DO - 10.3324/haematol.2018.209536 UR - https://haematologica.org/article/view/9175 SP - 2519-2527 AB - 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. ER -