Complement activation during low-density lipoprotein apheresis.

Area of Science:

• Biochemistry
• Immunology
• Medical Devices

Background:

• Familial homozygous hypercholesterolemia is a severe genetic disorder requiring intensive treatment.
• Lipid apheresis is a treatment option for hypercholesterolemia, but its interaction with the immune system is not fully understood.

Purpose of the Study:

• To investigate complement system activation during lipid apheresis sessions in patients with familial homozygous hypercholesterolemia.
• To assess the levels of complement components and byproducts in blood and within the extracorporeal circulation device.

Main Methods:

• Two patients with familial homozygous hypercholesterolemia underwent apheresis using LA15 or LA40 (Kaneka liposorber).
• Blood levels of C3c, C3a, and leukocyte counts were measured.
• Plasma levels of C3c and C3a were analyzed within the extracorporeal circuit.
• Sequential eluates from the LA40 device were collected and analyzed for complement fragments.

Main Results:

• Anaphylatoxin C3a levels increased during apheresis, particularly with the LA40 device.
• Nonnative complement fragments bearing C3a and C3d antigens were detected in eluates, suggesting in situ complement activation.
• Despite trapping in the dextran column, C3a was present in efferent plasma.

Conclusions:

• Lipid apheresis, specifically with the Kaneka liposorber, can induce complement system activation.
• This activation poses a potential risk during treatment and may lead to long-term side effects.
• Further research is needed to mitigate complement activation during extracorporeal circulation procedures.