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. 2016 Jan 18:7:1-4.
doi: 10.2147/JBM.S93008. eCollection 2016.

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 Tanimoto  2
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Relationship between HMGB1 and PAI-1 after allogeneic hematopoietic stem cell transplantation

Shosaku Nomura et al. J Blood Med. .

Abstract

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: HMGB1; PAI-1; TBI; aHSCT; transplantation-associated coagulopathy.

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Figures

Figure 1
Figure 1
The comparison of HMGB1 levels. Note: Data are shown as means ± SD. Abbreviations: TBI, total body irradiation; CY, cyclophosphamide; Flu, fludarabine; Bu, busulfan; BMT, bone marrow transplantation; PBSCT, peripheral blood stem cell transplantation; CBT, cord blood transplantation; Cys, cyclosporine; FK, tacrolimus; NS, not significant; HMGB1, high-mobility group box 1; SD, standard deviation.
Figure 2
Figure 2
Changes in PAI-1 levels following aHSCT conditioning regimens with and without significant elevation in HMGB1. Notes: Group A: HMGB1 levels >1.5-fold higher than baseline. Group B: HMGB1 levels <1.5-fold higher than baseline. *P-values are for comparison with each baseline parameter (before vs day 0, 4, 7, 14, 21, or 28); **Group A vs Group B. Abbreviations: PAI-1, plasminogen activator inhibitor-1; aHSCT, allogeneic hematopoietic stem cell transplantation; HMGB1, high-mobility group box 1; NS, not significant.
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