Complement fixation in acute serum sickness: assembly of glomerular-bound C3-convertase

Area of Science:

• Immunology
• Nephrology
• Complement System Biology

Background:

• Glomerular immune deposits are implicated in nephritis pathogenesis.
• The role of complement activation pathways in acute serum sickness (ASS) requires detailed investigation.

Purpose of the Study:

• To elucidate the complement (C) fixing properties of glomerular immune deposits in acute serum sickness (ASS) in vitro.
• To determine the predominant complement pathway involved in glomerular C deposition during ASS.

Main Methods:

• In vitro study using two groups of rabbits with ASS: decomplemented (cobra venom factor-treated) and non-decomplemented.
• Perfusion of rabbit kidneys with complement-deficient or pathway-inhibited sera to assess C3 fixation.
• Incubation of kidney sections with purified complement factors and human/guinea-pig C3 to evaluate deposition.

Main Results:

• C3 fixation occurred in both classical and alternative pathway assays in Group I (decomplemented) rabbits, but not with EDTA-treated serum.
• In Group II (non-decomplemented) rabbits, C3 fixation to deposits was observed with factors B and D, indicating alternative pathway involvement.
• Pre-incubation with C3b-inactivator reduced C3 fixation, while depletion of factor D from classical pathway components abolished it.

Conclusions:

• Glomerular complement deposition in acute serum sickness is predominantly driven by alternative pathway activation (C3b-feedback).
• This alternative pathway-dependent complement fixation is progressively lost during the nephritis evolution in ASS.
• Findings highlight the dynamic role of complement pathways in the immunopathology of acute serum sickness.