Abnormal immune complex processing and spontaneous glomerulonephritis in complement factor H-deficient mice with...

Area of Science:

• Immunology
• Nephrology
• Complement System Biology

Background:

• Complement receptor 1 (CR1) on erythrocytes and complement factor H (CFH) on platelets mediate immune adherence for immune complex (IC) processing.
• Similar immune adherence functions exist in glomerular podocytes, with CR1 in humans and CFH in rodents.

Purpose of the Study:

• To investigate the role of CR1 and CFH in immune complex processing and glomerulonephritis using a mouse model.
• To understand the complexities of complement-dependent IC processing in blood cells and the glomerulus.

Main Methods:

• Studied transgenic mice lacking systemic CFH but expressing human CR1 on erythrocytes (CR1(hu)Tg/CFH(-/-)).
• Utilized a chronic serum sickness model involving active immunization with heterologous apoferritin.
• Analyzed IC deposition, complement activation, and glomerulonephritis development.

Main Results:

• CR1(hu)Tg/CFH(-/-) mice spontaneously developed proliferative glomerulonephritis.
• Glomerulonephritis was accelerated by chronic serum sickness induction.
• ICs bound to erythrocytes, leading to increased glomerular IC deposition due to CR1 presence and absent platelet/podocyte CFH.
• Absence of plasma CFH resulted in complement activation by accumulated ICs, causing glomerulonephritis.

Conclusions:

• The study demonstrates the critical role of CFH as a plasma complement regulator.
• Highlights the intricate interplay of complement-mediated IC processing by erythrocytes and its impact on glomerular health.
• Emphasizes the significance of CFH in preventing spontaneous and IC-induced glomerulonephritis.