Plasma Adsorption Membranes Are Able to Efficiently Remove High Mobility Group Box-1 (HMGB-1).

Abstract

High Mobility Group Box 1 (HMGB-1) is a 30 kDa protein that is a lethal mediator in sepsis and is a recognized therapeutic target. However, no consensus has been reached for acute blood purification therapy as a treatment for sepsis targeting HMGB-1. Previous studies demonstrated that a high anti-HMGB-1 antibody titer and the suppression of HMGB-1 activity improved survival rate in animal sepsis models. The aim of this study was to evaluate whether plasma adsorption therapy is able to decrease the level of HMGB-1, representing a new potential treatment strategy against sepsis. Plasma adsorption therapy has been known as a treatment for various autoimmune diseases. Three different adsorbent columns, including TR-350 (IM-TR), PH-350 (IM-PH), and BRS-350 (BRS), were used in this study for comparison. We made a 1/350 scale of these three columns. Fetal bovine serum (FBS) contains a significant amount of HMGB-1. After priming with saline, FBS was passed through the columns and the adsorption rates of HMGB-1 at 25 minutes, 50 minutes, and 75 minutes were evaluated. The total adsorbed HMGB-1 level at 75 minutes was also calculated. The highest adsorption rate and total adsorbed amount of HMGB-1 were observed in IM-TR, followed by BRS and IM-PH. IM-TR showed a decline in adsorption rate over time. BRS showed a steady adsorption rate at all time points. IM-TR removed HMGB-1 significantly more than IM-PH and BRS. Our findings showed that plasma adsorption therapy efficiently adsorbed HMGB-1 and could be safely applied for the treatment of sepsis.