Relationship between HMGB1 and PAI-1 after allogeneic hematopoietic stem cell transplantation

Shosaku Nomura,1 Yoshinobu Maeda,2 Kazuyoshi Ishii,1 Yuta Katayama,3 Hideo Yagi,4 Naoto Fujishima,5 Shuichi Ota,6 Masato Moriyama,7 Takayuki Ikezoe,8 Yasuhiko Miyazaki,9 Kunio Hayashi,10 Shinya Fujita,1 Atsushi Satake,1 Tomoki Ito,1 Taiichi Kyo,3 Mitsune Tanimoto2 1First Department of Internal Medicine, Kansai Medical University, Hirakata, 2Department of Hematology and Oncology, Okayama University, Okayama, 3Division of Hematology, Hiroshima Red Cross Hospital, Hiroshima, 4Division of Hematology, Kidai Nara Hospital, Ikoma, 5Department of Hematology, Naphrology, and Rheumatology, Akita University, Akita City, 6Division of Hematology, Sapporo Hokuyu Hospital, Sapporo, 7Department of Hematology, Niigata University, Niigata, 8Department of Hematology and Respiratory Medicine, Kochi University, Nankoku, 9Division of Hematology, Oita Hospital, Oita, 10Division of Hematology, Meiwa Hospital, Nishinomiya, Japan Background: Conditioning regimens including total body irradiation (TBI) or cyclophosphamide can mobilize high-mobility group box 1 (HMGB1) to peripheral blood. Additionally, increased plasminogen activator inhibitor (PAI)-1 levels are associated with post-allogeneic hematopoietic stem cell transplantation (aHSCT). However, changes to circulating levels of HMGB1 after aHSCT are poorly understood. Materials and methods: The study cohort included 289 patients who underwent aHSCT at one of 25 institutions in Japan. We have investigated the relationship between HMGB1 and PAI-1 following aHSCT. A significant increase in HMGB1 levels occurred after conditioning treatment. Additionally, levels of HMGB1 at day 0 were significantly increased in TBI+ patients and cyclophosphamide/TBI patients. Conclusion: Our data revealed that an increased level of HMGB1 at day 0 following aHSCT correlates with increased PAI-1 after aHSCT, which is consistent with previous reports. Increased HMGB1 at day 0 after a conditioning regimen may play a role in transplantation-associated coagulopathy following aHSCT, because PAI-1 can accelerate procoagulant activity. Keywords: PAI-1, transplantation-associated coagulopathy, aHSCT, TBI, HMGB1