Top

Intensive Care Medicine

Published in:

01-06-2011 | Original

Emergence of autoantibodies to HMGB1 is associated with survival in patients with septic shock

Authors: Stéphanie Barnay-Verdier, Lakhdar Fattoum, Chloé Borde, Srini Kaveri, Sébastien Gibot, Vincent Maréchal

Published in: Intensive Care Medicine | Issue 6/2011

Abstract

Purpose

To assess the prevalence and predictive value of natural autoantibodies to high-mobility group box 1 (HMGB1) during sepsis.

Methods

Anti-HMGB1 and anti-human serum albumin (HSA) autoantibodies were detected by ELISA in 178 plasma samples longitudinally collected from 40 critically ill patients with septic shock. One hundred thirty-two plasma samples from healthy donors were used as control.

Results

IgGs to HMGB1 were detected in 15/40 patients (37.5%). The prevalence of anti-HMGB1 antibodies was significantly higher in the patients who survived (55%) compared to the patients who did not (20%) (p < 0.0001). The detection of anti-HMGB1 antibodies during the course of the disease was significantly associated with patient survival (p = 0.038). Moreover, there is a progressive and significant emergence of anti-HMGB1 antibodies during the course of the disease, mostly in patients who survived.

Conclusions

This study shows that autoantibodies to HMGB1 are produced during sepsis and are associated with a favorable outcome in patients undergoing septic shock.

Stros M (2010) HMGB proteins: interactions with DNA and chromatin. Biochim Biophys Acta 1799:101–113PubMed

Yang H, Tracey KJ (2009) Targeting HMGB1 in inflammation. Biochim Biophys Acta 1799:149–156PubMed

Bianchi ME (2009) HMGB1 loves company. J Leuk Biol 86:573–576CrossRef

Scaffidi P, Misteli T, Bianchi ME (2002) Release of chromatin protein HMGB1 by necrotic cells triggers inflammation. Nature 418:191–195PubMedCrossRef

Thorburn J, Horita H, Redzic J, Hansen K, Frankel AE, Thorburn A (2009) Autophagy regulates selective HMGB1 release in tumor cells that are destined to die. Cell Death Differ 16:175–183PubMedCrossRef

Bell CW, Jiang W, Reich CF 3rd, Pisetsky DS (2006) The extracellular release of HMGB1 during apoptotic cell death. Am J Physiol Cell Physiol 291:C1318–C1325PubMedCrossRef

Rauvala H, Rouhiainen A (2010) Physiological and pathophysiological outcomes of the interactions of HMGB1 with cell surface receptors. Biochim Biophys Acta 1799:164–170PubMed

Tsung A, Klune JR, Zhang X, Jeyabian G, Cao Z, Peng X, Stolz Geller DA, Rosengart MR, Billiar TR (2007) HMGB1 release induced by liver ischemia involves toll-like receptor 4 dependent reactive oxygen species production and calcium-mediated signaling. J Exp Med 204:2913–2923PubMedCrossRef

Yu M, Wang H, Ding A, Golenbock DT, Latz E, Czura CJ, Fenton MJ, Tracey KJ, Yang H (2006) HMGB1 signals through toll-like recpetor (TLR) 4 and TLR2. Shock 26:174–179PubMedCrossRef

10.

Wang H, Bloom O, Zhang M, Vishnubhakat JM, Ombrellino M, Che J, Frazier A, Yang H, Ivanova S, Borovikova L, Manogue KR, Faist E, Abraham E, Andersson J, Andersson U, Molina PE, Abumrad NN, Sama A, Tracey KJ (1999) HMG-1 as a late mediator of endotoxin lethality in mice. Science 285:248–251PubMedCrossRef

11.

Ueno H, Matsuda T, Hashimoto S, Amaya F, Kitamura Y, Tanaka M, Kobayashi A, Maruyama I, Yamada S, Hasegawa N, Soejima J, Koh H, Ishizaka A (2004) Contributions of high mobility group box protein in experimental and clinical acute lung injury. Am J Respir Crit Care Med 170:1310–1316PubMedCrossRef

12.

Sunden-Cullberg J, Norrby-Teglund A, Rouhiainen A, Rauvala H, Herman G, Tracey KJ, Lee ML, Andersson J, Tokics L, Treutiger CJ (2005) Persistent elevation of high mobility group box-1 protein (HMGB1) in patients with severe sepsis and septic shock. Crit Care Med 33:564–573PubMedCrossRef

13.

Gibot S, Massin F, Cravoisy A, Barraud D, Nace L, Levy B, Bollaert PE (2007) High-mobility group box 1 protein plasma concentrations during septic shock. Intensive Care Med 33:1347–1353PubMedCrossRef

14.

Watanabe M, Uchida K, Nakagaki K, Kanazawa H, Trapnell BC, Hoshino Y, Kagamu H, Yoshizawa H, Keicho N, Goto H, Nakata K (2007) Anti-cytokine autoantibodies are ubiquitous in healthy individuals. FEBS Lett 581:2017–2021PubMedCrossRef

15.

Bakhiet M, Diab A, Mahamustafa Jiezhu, Lindqvist L, Link H (1997) Potential role of autoantibodies in the regulation of cytokine responses during bacterial infections. Infect Immun 65:3300–3303PubMed

16.

Thierry S, Gozlan J, Jaulmes A, Boniface R, Nasreddine N, Strauss F, Marechal V (2007) High-mobility group box 1 protein induces HIV-1 expression from persistently infected cells. AIDS 21:283–292PubMedCrossRef

17.

Avrameas S, Guilbert B, Dighiero G (1981) Natural antibodies against tubulin, actin myoglobin, thyroglobulin, fetuin, albumin and transferrin are present in normal human sera, and monoclonal immunoglobulins from multiple myeloma and Waldenström’s macroglobulinemia may express similar antibody specificities. Ann Immunol (Paris) 132C:231–236

18.

Angus DC, Yang L, Kong L, Kellum JA, Delude RL, Tracey KJ, Weissfeld L (2007) Circulating high-mobility group box 1 (HMGB1) concentrations are elevated in both uncomplicated pneumonia and pneumonia with severe sepsis. Crit Care Med 35:1061–1067PubMedCrossRef

19.

Karlsson S, Pettila V, Tenhunen J, Laru-Sompa R, Hynninen M, Ruokonen E (2008) HMGB1 as a predictor of organ dysfunction and outcome in patients with severe sepsis. Intensive Care Med 34:1046–1053PubMedCrossRef

20.

Fomsgaard A, Zhang GH, Shand GH, Bendtzen K, Baek L (1989) Immunochemical and biological reactivity of human anti-lipopolysaccharide IgG obtained by screening of blood donors. Scand J Immunol 29:309–316PubMedCrossRef

21.

Lacroix-Desmazes S, Bayry J, Kaveri SV, Hayon-Sonsino D, Thorenoor N, Charpentier J, Luyt CE, Mira JP, Nagaraja V, Kazatchkine MD, Dhainaut JF, Mallet VO (2005) High levels of catalytic antibodies correlate with favorable outcome in sepsis. Proc Natl Acad Sci USA 102:4109–4113PubMedCrossRef

22.

Urbonaviciute V, Furnrohr BG, Weber C, Haslbeck M, Wilhelm S, Herrmann M, Voll RE (2007) Factors masking HMGB1 in human serum and plasma. J Leuk Biol 81:67–74CrossRef

Title: Emergence of autoantibodies to HMGB1 is associated with survival in patients with septic shock
Authors: Stéphanie Barnay-Verdier
Lakhdar Fattoum
Chloé Borde
Srini Kaveri
Sébastien Gibot
Vincent Maréchal
Publication date: 01-06-2011
Publisher: Springer-Verlag
Published in: Intensive Care Medicine / Issue 6/2011
Print ISSN: 0342-4642
Electronic ISSN: 1432-1238
DOI: https://doi.org/10.1007/s00134-011-2192-6

Keynote webinar | Spotlight on medication adherence

Springer Medicine

Emergence of autoantibodies to HMGB1 is associated with survival in patients with septic shock

Abstract

Purpose

Methods

Results

Conclusions

Keynote webinar | Spotlight on medication adherence

Springer Medicine

Abstract

Purpose

Methods

Results

Conclusions

Please log in to get access to this content

Other articles of this Issue 6/2011

The effect of etomidate on adrenal function in critical illness: a systematic review

Erratum to: Pulse pressure: more than 100 years of changes in stroke volume

A close look at proportions of pathogens associated with pneumonia

A modified technique for insertion of dual lumen bicaval cannulae for venovenous extracorporeal membrane oxygenation

Volatile agents for ICU sedation?

Optimisation of positive end-expiratory pressure by forced oscillation technique in a lavage model of acute lung injury