Ultrastructural localization of the membrane attack complex of complement in human renal tissues

Area of Science:

• Nephrology
• Immunology
• Complement System

Background:

• The membrane attack complex (MAC) is a key component of the complement system.
• Its role in kidney diseases, including diabetes and glomerulonephritis, requires further investigation.

Purpose of the Study:

• To investigate the deposition patterns of MAC in kidney tissues from healthy individuals and patients with specific kidney diseases.
• To correlate MAC deposition with disease severity and histological findings.

Main Methods:

• Immunoelectron microscopy (IEM) and immunofluorescent (IF) microscopy were employed.
• Monoclonal antibody (Poly C9-MA) targeting the C9 portion of MAC was used.
• Comparative analysis with polyclonal antibodies against complement components (C3, C5) and immunoglobulins (IgG, IgA, IgM) was performed.

Main Results:

• In normal kidneys, MAC deposition increased with age in mesangial stalks, tubular basement membranes (TBMs), and arteriolar walls.
• In insulin-dependent diabetes mellitus (IDDM), MAC deposition in the mesangium correlated with the degree of tissue damage.
• IEM revealed MAC on membranous structures within the mesangium, TBMs, vessel walls, and glomerular basement membranes (GBMs) in diabetic subjects, likely on cellular debris.
• In membranous glomerulonephritis (MPGN II), MAC and C3 were found within subepithelial and dense deposits in GBMs and TBMs.

Conclusions:

• MAC deposition is a common finding in normal aging kidneys and is significantly increased in diabetic nephropathy and MPGN II.
• The study provides evidence for MAC deposition in various kidney compartments, potentially contributing to renal pathology.
• Further research is warranted to elucidate the precise role of MAC in the pathogenesis of these kidney diseases.