Complement activation in thrombotic thrombocytopenic purpura.

Abstract

BACKGROUND:

Ultra-large von Willebrand factor and deficiency of its cleaving protease are important factors in the events leading to thrombotic microangiopathy; however, the mechanisms involved are only partly understood. Whereas pathological activation of the alternative complement pathway is linked to atypical hemolytic uremic syndrome, the role of complement activation in thrombotic thrombocytopenic purpura (TTP) is unknown. The aim of this study was to investigate whether signs of complement activation are characteristic of TTP.

PATIENTS AND METHODS:

Twenty-three patients with TTP (18 women, median age 38 years) and 17 healthy controls (13 women, median age 38 years) were included. Complement parameters (C3, Factors H, I, B and total alternative pathway activity) together with complement activation fragments (C3a) or complexes (C1rs-INH, C3bBbP, sC5b9) were measured by ELISA or RID. ADAMTS13 activity and anti-ADAMTS13 inhibitory antibodies were measured by the VWF-FRET73 assay.

RESULTS:

Increased levels of C3a, and SC5b9 were observed in TTP during acute episodes, as compared with healthy controls. Decreased complement C3 levels indicative of complement consumption occurred in 15% of acute TTP patients. Significant decrease of complement activation products C3a and SC5b9 was observed during plasma exchange (PEX). The sustained presence of anti-ADAMTS13 inhibitory antibodies in complete remission was associated with increased complement activation.

CONCLUSION:

These data document in an observational study the presence of complement activation in TTP. Further investigation is needed to determine its potential pathogenetic significance.

• Authors: M Réti, P Farkas, D Csuka, K Rázsó, Á Schlammadinger, M L Udvardy, K Madách, G Domján, C Bereczki, G S Reusz, A J Szabó, Z Prohászka
• Journal: Journal of thrombosis and haemostasis : JTH (J Thromb Haemost) Vol. 10 Issue 5 Pg. 791-8 (May 2012) ISSN: 1538-7836 [Electronic] England
• PMID: 22372946 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)
• Copyright: © 2012 International Society on Thrombosis and Haemostasis.

Chemical References

• Antibodies, Neutralizing
• Autoantibodies
• Biomarkers
• Complement System Proteins
• ADAM Proteins
• ADAMTS13 Protein
• ADAMTS13 protein, human

Topics

• ADAM Proteins (immunology)
• ADAMTS13 Protein
• Adult
• Antibodies, Neutralizing (blood)
• Autoantibodies (blood)
• Biomarkers (blood)
• Case-Control Studies
• Complement Activation
• Complement System Proteins (analysis)
• Enzyme-Linked Immunosorbent Assay
• Female
• Humans
• Hungary
• Male
• Middle Aged
• Plasma Exchange
• Purpura, Thrombotic Thrombocytopenic (blood, immunology, therapy)
• Radioimmunoassay