Naturally acquired anti-high mobility group box 1 antibodies during septic shock

Introduction

High mobility group box 1 (HMGB1) is a pleiotropic cytokine, implicated in the pathophysiology of sepsis. This alarmin, usually located in the nucleus, is released after tissue injury and activates various innate immunity receptors, leading to sustained inflammatory response. Inhibition of HMGB1 by anti-HMGB1 antibodies has been reported to decrease mortality in experimental models of sepsis. In the present work, we analyse whether HMGB1 secretion during septic shock leads to the production of naturally acquired anti-HMGB1 antibodies during septic shock.

Methods

All patients with septic shock criteria and no immunosuppression were included during a 6-month period of time. After informed consent, blood samples (200 μl) were drawn on the day of shock and at D3, D7, and D14. Plasma HMGB1 levels were measured, using a commercial ELISA kit (Sino-Test Corporation, Sagamihara, Japan). Auto anti-HMGB1 antibodies were detected in serum by a homemade ELISA test.

Results

Forty-two septic shock patients were included. Median age was 70 (59 to 78) years, SAPS 2 was 68 (51 to 83), and the mortality rate was 29%. HMGB1 was undetectable in the plasma of a control population. In contrast, high levels of HMGB1 were found in all septic patients (median = 5.71 ng/ml at D7). Thirteen patients (38%) presented a significant production of auto anti-HMGB1 IgG antibodies during the course of sepsis. The age, sex ratio, median HMGB1 level and mortality rate were similar in patients producing (PPAb) and not producing antibodies (PNPAb). However, as compared with the PNPAb patients, the PPAb group had significant higher APACHE II (P = 0.027) and SOFA scores (P = 0.02) at the onset of shock and had a more important but nonsignificant decrease of the cardiovascular SOFA score between day 1 and day 7 (P = 0.063).

Conclusion

Naturally acquired anti-HMGB1 antibodies are produced during septic shock. The presence of antibodies is associated with higher severity scores and might be associated with an improvement of the haemodynamic dysfunction. The neutralizing capacity of these autoantibodies and their physiological role remain to be investigated.