Complement deposition in renal allografts with early malfunction.

Area of Science:

• Nephrology
• Immunology
• Transplantation

Background:

• Early severe impairment of renal allograft function can be associated with specific complement deposition patterns.
• Previous work identified isolated complement factor C3 deposition in glomeruli of affected patients.

Purpose of the Study:

• To extensively study the pattern of complement deposition in renal allograft biopsies.
• To investigate the nature and localization of complement factor C3 deposition.
• To explore the potential mechanism of complement activation in these cases.

Main Methods:

• Immunofluorescence technique on allograft biopsies from five patients.
• Immunoelectron microscopy to determine the localization of C3 antigen.
• Analysis of various complement factors (C3, C4, C1q, Factor B, Properdin) and immunoglobulins (IgG, IgA, IgM).

Main Results:

• Prominent deposition of C3c, C3d, and C4d antigens in glomerular capillary walls.
• Positive reaction for vitronectin (S-protein); only trace amounts of C9 neoepitope.
• Absence of C1q, C4c, C3a, iC3b, Factor B, Properdin, and immunoglobulins.
• C3 antigen localized within the glomerular basement membrane via immunoelectron microscopy.

Conclusions:

• Glomerular C3 deposition primarily consists of C3b and/or C3c/C3d molecules.
• Complement activation occurs early in the classical pathway, despite the absence of detectable immunoglobulins.
• This pattern may represent a humoral rejection, potentially initiated by low-titer antibodies against endothelial antigens.