Contact activation-induced complex formation between complement factor H and coagulation factor XIIa

Area of Science:

• Biochemistry
• Immunology
• Vascular Biology

Background:

• Complement and coagulation systems share evolutionary origins and homologous components.
• Complement factor H (FH) and coagulation factor XII (FXII) possess auxiliary activities in their respective systems.

Purpose of the Study:

• To investigate the interaction between coagulation factor XII (FXII) and complement factor H (FH).

Main Methods:

• Enzyme-linked immunosorbent assay (ELISA) and surface plasmon resonance (SPR) were used to study complex formation.
• Plasma samples were analyzed using ELISA and immunoprecipitation to detect α-FXIIa:FH complexes upon contact activation.

Main Results:

• A direct interaction was identified between activated FXII (α-FXIIa) and FH, with an apparent binding strength (Kd) of 34 ± 9 nmol/L.
• Complex formation involved the kringle domain of α-FXIIa's heavy chain and occurred in normal human plasma after contact activation.
• Elevated α-FXIIa:FH complexes were found in hereditary angioedema (HAE) patients, while rheumatoid arthritis (RA) patients showed levels similar to healthy individuals.

Conclusions:

• A direct interaction between α-FXIIa and FH has been demonstrated.
• This finding highlights a novel crosstalk between the complement and coagulation systems.
• This interaction may be significant in the pathogenesis of inflammatory vascular diseases.