Plasma concentrations and importance of high mobility group box protein in the prognosis of organ failure in patients with disseminated intravascular coagulation

Tsuyoshi Hatada; Hideo Wada; Tsutomu Nobori; Kazuhiro Okabayashi; Kazuo Maruyama; Yasunori Abe; Shinji Uemoto; Shingo Yamada; Ikuro Maruyama

doi:10.1160/TH05-05-0316

Thrombosis and Haemostasis, Table of Contents

Thromb Haemost 2005; 94(05): 975-979
DOI: 10.1160/TH05-05-0316

Blood Coagulation, Fibrinolysis and Cellular Haemostasis

Schattauer GmbH

Plasma concentrations and importance of high mobility group box protein in the prognosis of organ failure in patients with disseminated intravascular coagulation

Tsuyoshi Hatada

¹Department of Emergency Medicine, Mie University School of Medicine, Mie, Japan

,

Hideo Wada

²Department of Laboratory Medicine, Mie University School of Medicine, Mie, Japan

,

Tsutomu Nobori

²Department of Laboratory Medicine, Mie University School of Medicine, Mie, Japan

,

Kazuhiro Okabayashi

³Department of Anesthesiology, Mie University School of Medicine, Mie, Japan

,

Kazuo Maruyama

³Department of Anesthesiology, Mie University School of Medicine, Mie, Japan

,

Yasunori Abe

⁴Department of Central Laboratory, Mie University School of Medicine, Mie, Japan

,

Shinji Uemoto

⁵First Department of Surgery, Mie University School of Medicine, Mie, Japan

,

Shingo Yamada

⁶Central Institute, Shino-Test Co., Tokyo, Japan

,

Ikuro Maruyama

⁷Vascular medicine, Kagoshima University Graduate School and Dental Science, Kagoshima, Japan

› Author Affiliations

Abstract

Summary

High Mobility Group Box chromosomal protein 1 (HMGB1) is a nuclear DNA-binding protein acting as a proinflammatory cytokine when released in the extracellular space from necrotic cells, activated macrophages and dendritic cells. HMGB1 acts on a specific receptor, RAGE (receptor for advanced glycation endproducts), and induces prolonged inflammation, organ failure, septicaemia and death. The aim of the study was to determine the diagnostic value of plasma HMGB1 concentration and its role in the development of organ failure in patients with disseminated intravascular coagulation (DIC). Plasma HMGB-1 levels were measured in patients with suspected DIC and their relationships with DIC, organ failure and clinical outcome were determined. The study took place at the intensive care facility, Mie University School of Medicine and comprised 201 patients with suspected DIC. Plasma HMGB1 was below the detection limit in normal subjects, but moderately elevated in patients with infectious diseases (4.54 ± 8.18 ng/ml, mean±SD), malignancies (2.15 ± 5.34 ng/ml), and traumas (6.47 ± 13.13 ng/ml). DIC was associated with significantly high plasma HMGB1 (14.05 ± 12.56 ng/ml) in these patients. The highest HMGBI levels were in patients with organ failure (8.29 ± 10.99 ng/ml) and non-survivors (16.58 ± 11.01 ng/ml). HMGB1 plasma levels correlated with the DIC score and sepsis-related organ failure assessment (SOFA) score. In conclusion, our data suggest that HMGB-1 is a potentially suitable prognostic marker of OF or DIC.

Keywords

HMGB-1 - DIC - organ failure

Full Text

References

References
1 Bustin M. Regulation of DNA-dependent activities by the functional motifs of the high mobility-group chromosomal proteins. Mol Cell Biol 1999; 19: 5237-46.
2 Parkkinen J, Raulo E, Merenmies J. et al. Amphoterin, 30-kDa protein in a family of HMG-1 type polypeptides: enhanced expression in transformed cells, leading edge localization, and interactions with plasminogen activation. J Biol Chem 1993; 268: 19726-38.
3 Bianchi ME, Beltrame M. Flexing DNA:HMG-box proteins and their pattern. Am J Hum Genet 1998; 63: 1573-7.
4 Jayaraman L, Moorthy NC, Murthy KG. et al. High mobility group protein-1 (HMG-1) is a unique activator of p53. Gene Dev 1998; 12: 462-72.
5 Hori O, Brett J, Slattery T. et al. The receptor for advanced glycation end products (RAGE) is a cellular binding site for amphoterin: mediation of neurite outgrowth and co-expression of RAGE and amphoterin in the developing nervous system. J Biol Chem 1995; 270: 25752-61.
6 Parkkinen J, Rauvala H. Interactions of plasminogen and tissue plasminogen activator(t-PA) with amphoterin: Enhancement of t-PA catalyzed plasminogen activator by amphoterin. J Biol Chem 1991; 266: 1063-74.
7 Abraham E, Arcaroli J, Carmody A. et al. HMG-1 a mediator of acute lung inflammation. J Immunol 2000; 165: 2950-54.
8 Wang H, Bloom O, Zhang M. et al. HMG-1 as a late mediator of endotoxin lethality in mice. Science 1999; 285: 248-51.
9 Czura CJ, Wang H, Tracy K. Dual roles for HMGB1:DNA binding and cytokine. J. Endotoxin Res 2001; 7: 315-21.
10 Brickman JM, Adam M, Ptashne M. nteraction between an HMG-1 protein and members of the Rel family. Proc Natl Acad Sci 1999; 96: 10679-83.
11 Yamada S, Inoue K, Yakabe K. et al. High mobility group protein 1(HMGB1) quantified by ELISA with a monoclonal antibody that does not cross-react with HMGB1. Clin Chem 2003; 49: 1535-37.
12 Ueno H, Matsuda T, Hashimoto S. et al. Contributions of high mobility group box protein in experimental and clinical acute lung injury. Am J Respir Crit Care Med 2004; 170: 1310-6.
13 Taniguchi N, Kawahara K, Yone K. et al. High mobility group box chromosomal protein 1 plays a role in the pathogenesis of rheumatoid arthritis as a novel cytokine. Arthritis Rheum 2003; 48: 971-81.
14 Vincent JL, Moreno R, Takahara J. The SOFA (sepsis- related organ failure assessment) score to describe organ dysfunction/failure. Intensive Care Med 1996; 22: 707-10.
15 Wada H, Gabazza EC, Asakura H. et al. Comparison of diagnostic criteria for disseminated intravascular coagulation (DIC): diagnostic criteria of the International Society of Thrombosis and Haemostasis (ISTH) and of the Japanese Ministry of Health and Welfare for overt- DIC. Am J Hematol 2003; 74: 17-22.
16 Bone RC. Toward an epidemiology and natural history of SIRS (systemic inflammatory response syndrome). JAMA 1992; 268: 3452-5.
17 Wada H, Gabazza EC, Asakura H. et al. Comparison of diagnostic criteria for disseminated intravascular coagulation (DIC): diagnostic criteria of the International Society of Thrombosis and Haemostasis (ISTH) and of the Japanese Ministry of Health and Welfare for overt- DIC. Am J Hematol 2003; 74: 17-22.
18 Watanabe R, Wada H, Miura Y. et al. Plasma levels of total plasminogen activator inhibitor-I and tissue plasminogen activator/inhibitor complex in patients with disseminated intravascular coagulation and thrombotic thrombocytopenic purpura. Clin Appl Thromb Haemost 2001; 7: 229-33.
19 Wada H, Tomeoku M, Deguchi A. et al. Anticoagulant activity in cell homogenate of adult T cell leukemia. Thromb Haemost 1988; 59: 197-201.
20 Ombrellino M, Wang H, Ajemian MS. et al. Increased serum concentrations of high-mobility-group protein 1 in haemorrhagic shock. Lancet 1999; 354: 1446-7.
21 Wada H, Tamaki S, Tanigawa M. et al. Plasma level of IL-1β in disseminated intravascular coagulation. Thromb Haemost 1991; 65: 364-8.
22 Wada H, Ohiwa M, Kaneko T. et al. Plasma level of tumor necrosis factor in disseminated intravascular coagulation. Am J Hematol 1991; 37: 147-51.
23 Wada H, Tanigawa M, Wakita Y. et al. Increased plasma level of interleukin-6 in disseminated intravascular coagulation. Blood Coagul Fibrinolysis 1993; 4: 583-90.
24 Wang H, Yang H, Tracey KJ. Extracellular role of HMGB1 in inflammation and sepsis. J Intern Med 2004; 255: 320-31.
25 Taylor Jr FB, Toh CH, Hoots WK. et al. Towards definition, clinical and laboratory criteria, and a scoring system for disseminated intravascular coagulation – On behalf of the Scientific Subcommittee on disseminated intravascular coagulation (DIC) of the International Society on Thrombosis and Haemostasis (ISTH). Thromb Haemost 2001; 86: 1327-30.
26 Abeyama K, Stern DM, Ito Y. The N-terminal domain of thrombomodulin sequetesters high mobility group-B1 protein, a novel anti-inflammatory mechanism. J Clin Invest 2005; 115: 1267-74.
27 Kapiotis S, Besemer J, Bevec D. et al. Interleukin-4 counteracts pyrogen-induced downregulation of thrombomodulin in cultured human vascular endothelial cells. Blood 1991; 78: 410-5.
28 Kim JY, Park JS, Strassheim D. et al. HMGB1 contributes to the development of acute lung injury after hemorrhage. Am J Physiol Lung Cell Mol Physiol 2005; 288: L958-65.
29 Fiuza C, Bustin M, Talwar S. et al. Inflammationpromoting activity of HMGB1 on human microvascular endothelial cells. Blood 2003; 101: 2652-60.
30 Okabayashi K, Wada H, Ohta S. et al. Hemostatic markers and the sepsis-related organ failure assessment score in patients with disseminated intravascular coagulation in an intensive care unit. Am J Hematol 2004; 76: 225-9.