Complement and cytokine response in acute Thrombotic Thrombocytopenic Purpura

Br J Haematol. 2014 Mar;164(6):858-66. doi: 10.1111/bjh.12707. Epub 2013 Dec 28.


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.

Keywords: ADAMTS13; T cells; Thrombotic Thrombocytopenic Purpura; complement; cytokines.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • ADAM Proteins / immunology
  • Adolescent
  • Adult
  • Aged
  • Atypical Hemolytic Uremic Syndrome
  • Cohort Studies
  • Complement Activation / immunology*
  • Cytokines / immunology*
  • Female
  • Hemolytic-Uremic Syndrome / immunology*
  • Hemolytic-Uremic Syndrome / pathology
  • Humans
  • Male
  • Middle Aged
  • Prospective Studies
  • Purpura, Thrombotic Thrombocytopenic / immunology*
  • Purpura, Thrombotic Thrombocytopenic / pathology
  • Young Adult


  • Cytokines
  • ADAM Proteins