Complement and cytokine response in acute Thrombotic

Complement dysregulation is key in the pathogenesis of atypical Haemolyt-ic Uraemic Syndrome (aHUS), but no clear role for complement has been identified in Thrombotic Thrombocytopenic Purpura (TTP). We aimed to assess complement activation and cytokine response in acute antibody-mediated TTP. Complement C3a and C5a and cytokines (interleukin (IL)-2, IL-4, IL-6, IL-10, tumour necrosis factor, interferon-c and IL-17a) were measured in 20 acute TTP patients and 49 remission cases. Anti-ADAM-TS13 immunoglobulin G (IgG) subtypes were measured in acute patients in order to study the association with complement activation. In acute TTP, median C3a and C5a were significantly elevated compared to remis-sion, C3a 639 ng/ml vs. 382 ng/ml (P < 0001) and C5a 164 ng/ml vs. 929 ng/ml (P < 0001), respectively. Median IL-6 and IL-10 levels were significantly higher in the acute vs. remission groups, IL-6: 8 pg/ml vs. 2 pg/ml (P = 0003), IL-10: 6 pg/ml vs. 2 pg/ml (P < 0001). C3a levels correlated with both anti-ADAMTS13 IgG (rs = 0604, P = 0017) and IL-10 (rs = 0692, P = 0006). No anti-ADAMTS13 IgG subtype was associ-ated with higher complement activation, but patients with the highest C3a levels had 3 or 4 IgG subtypes present. These results suggest complement anaphylatoxin levels are higher in acute TTP cases than in remission, and the complement response seen acutely may relate to anti-ADAMTS13 IgG antibody and IL-10 levels