Immunohistochemical study of the membrane attack complex of complement in IgA nephropathy

Area of Science:

• Nephrology
• Immunology
• Pathology

Background:

• Primary IgA nephropathy is a common cause of glomerulonephritis.
• The role of the complement system in IgA nephropathy pathogenesis is not fully understood.
• The terminal complement pathway, specifically the membrane attack complex (MAC), may play a role.

Purpose of the Study:

• To investigate the localization and deposition patterns of MAC in human IgA nephropathy kidneys.
• To determine the association of MAC deposition with other immune deposits and complement components.
• To elucidate the complement pathway involved in MAC formation in IgA nephropathy.

Main Methods:

• Immunofluorescence microscopy was used to detect MAC deposition in kidney biopsies.
• Immunoelectron microscopy provided detailed ultrastructural localization of MAC.
• Dual-staining techniques identified co-localization with IgA, IgG, C3, C5, and C9.

Main Results:

• MAC deposition was significantly increased in IgA nephropathy kidneys compared to normal controls.
• MAC deposits were found in the mesangium and glomerular capillary walls in most patients.
• MAC co-localized with IgA, C3, C5, and C9, suggesting complement activation.
• Immunoelectron microscopy revealed diverse MAC staining patterns, including within electron-dense deposits and associated with striated membrane structures.

Conclusions:

• The terminal complement pathway is activated in IgA nephropathy, likely via the alternative pathway.
• MAC deposition in the mesangium is associated with paramesangial lesions and electron-dense deposits.
• In situ complement activation may contribute to MAC deposition in glomerular structures.