Adsorption of complement factor D by polyacrylonitrile dialysis membranes

Area of Science:

• Biochemistry
• Immunology
• Nephrology

Background:

• Factor D is crucial for the alternative pathway (AP) of complement.
• Factor D levels increase in end-stage renal failure (ESRF).
• Polyacrylonitrile (PAN) membranes poorly activate complement and adsorb C3a.

Purpose of the Study:

• To investigate the adsorption of factor D by PAN membranes.
• To determine if factor D retains its activity after adsorption.

Main Methods:

• In vitro incubation of normal human serum (NHS) and purified radiolabeled factor D with PAN and cuprophan (Cu) fibers.
• Hemolytic assays to measure factor D activity.
• Passage of NHS and whole blood through PAN dialyzers.
• Elution and immunoblotting of proteins from used PAN filters.
• Comparison of factor D levels in patients dialyzed with PAN versus cellulose acetate.

Main Results:

• PAN fibers adsorbed hemolytic factor D from NHS in vitro, while cuprophan did not.
• Purified factor D bound to PAN in a dose- and time-dependent manner.
• Factor D adsorbed to PAN lost hemolytic activity.
• PAN dialyzers removed 95% of factor D from NHS and whole blood.
• Significant amounts of active factor D were eluted from used PAN filters.
• Dialysis with PAN reduced blood factor D levels by 81.4% in ESRF patients, compared to 9.6% with cellulose acetate.
• PAN removed factor D primarily through adsorption, not elimination in dialysis fluid.

Conclusions:

• PAN membranes possess a significant capacity to adsorb factor D.
• This adsorption may contribute to the reduced AP activation by PAN membranes.
• The clinical benefit of factor D removal in uremic patients requires further investigation.