Complement dysregulation is key in the pathogenesis of atypical Haemolytic 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-γ and IL-17a) were measured in 20 acute
TTP patients and 49 remission cases. Anti-ADAMTS13
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 remission, C3a 63·9 ng/ml vs. 38·2 ng/ml (P < 0·001) and C5a 16·4 ng/ml vs. 9·29 ng/ml (P < 0·001), 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 = 0·003), IL-10: 6 pg/ml vs. 2 pg/ml (P < 0·001). C3a levels correlated with both anti-ADAMTS13
IgG (rs = 0·604, P = 0·017) and
IL-10 (rs = 0·692, P = 0·006). No anti-ADAMTS13
IgG subtype was associated 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.