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Defective Fc-dependent processing of immune complexes in patients with systemic lupus erythematosus
Kevin A Davies1, Michael G Robson, A Michael Peters
1Division of Medicine, Imperial College School of Medicine at Hammersmith Hospital, London, UK. kevin.davies@ic.ac.uk
Objective:
To explore the Fc receptor-dependent handling of immune complexes (ICs) by the fixed mononuclear phagocytic systems (MPS) in patients with systemic lupus erythematosus (SLE).
Methods:
The processing in vivo of soluble model (123)I-hepatitis B/ anti-hepatitis B ICs was studied in 12 healthy subjects and 10 patients with active SLE. ICs that fixed complement poorly were prepared specifically in order to explore Fc receptor-dependent clearance mechanisms. Clearance kinetics and organ uptake were assessed by computer-aided gamma scintigraphy and serial blood sampling.
Results:
In both patients and controls, the main site of IC clearance was the liver; only 2-6% of injected ICs were taken up in the spleen. The kinetics of initial IC clearance were similar in both groups, but defective hepatic retention of ICs was demonstrated in patients with SLE. At 1 hour, hepatic activity in patients had fallen to 56% of maximum, compared with 74% in controls (P = 0.0002). Precipitation studies performed on serum samples using staphylococcal protein A-Sepharose indicated that antibody-complexed tracer was released from the liver 20-50 minutes after injection.
Conclusion:
These results indicate that Fc-mediated clearance of ICs is defective in patients with SLE and suggest that ligation of ICs by Fc receptors is critical for their efficient binding and retention by the fixed MPS in the liver.