SCD increases plasma HMGB1 and TLR4 receptor activity in humans. (A) Plasma concentrations of HMGB1 in control and SCD individuals (n = 19, 26, respectively, **P = .047); (B) HMGB1 concentrations in plasma from SCD individuals at baseline and crisis (n = 19, *P = .0362); (C) Total TLR4 receptor activity induced by control and SCD plasma (n = 12, *P < .05, ***P < .01); (D) HMGB1-dependent TLR4 receptor activity in plasma from SCD individuals at baseline and crisis. Data represent TLR4 reporter cell activity inhibited by pretreating plasma with anti-HMGB1 antibodies (n = 12, *P < .05); and (E) HMGB1-dependent TLR4 receptor activity represented as a percentage of total TLR4 receptor activity (n = 11 to 12, ***P < .01).