Defective Fc‐dependent processing of immune complexes in patients with systemic lupus erythematosus

• Published in: Arthritis and rheumatism Vol. 46; no. 4; pp. 1028 - 1038
• Main Authors: Davies, Kevin A., Robson, Michael G., Peters, A. Michael, Norsworthy, Peter, Nash, Julian T., Walport, Mark J.
• Format: Journal Article
• Language: English
• Published: New York Wiley Subscription Services, Inc., A Wiley Company 01.04.2002; Wiley
• Subjects: Adult; Antigen-Antibody Complex - chemistry; Antigen-Antibody Complex - immunology; Antigen-Antibody Complex - metabolism; Biological and medical sciences; Centrifugation, Density Gradient; Complement Activation; Complement System Proteins - analysis; Dermatology; Erythrocytes - chemistry; Erythrocytes - metabolism; Female; Humans; Liver - immunology; Liver - metabolism; Lupus Erythematosus, Systemic - immunology; Lupus Erythematosus, Systemic - metabolism; Male; Medical sciences; Microspheres; Molecular Weight; Protein Binding - immunology; Receptors, Complement 3b - analysis; Receptors, Complement 3b - metabolism; Receptors, Fc - immunology; Receptors, Fc - metabolism; Skin involvement in other diseases. Miscellaneous. General aspects; Spleen - immunology; Spleen - metabolism; Staphylococcal Protein A - immunology; Staphylococcal Protein A - metabolism; Sucrose; Human; Immunopathology; Connective tissue disease; Skin disease; Pathophysiology; Autoimmune disease; Mononuclear cell; Systemic disease; Lupus erythematosus; Disseminated; Phagocytosis; Immune complex; Biological receptor
• DOI: 10.1002/art.10189
• ISSN: 0004-3591

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 123I–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.