Splenic uptake of immune complexes in man is complement-dependent.
We have examined the effects of hereditary homozygous C2 deficiency on the processing of radiolabeled soluble immune complexes (IC). A patient with C2 deficiency was studied before and after treatment with fresh frozen plasma (FFP). Hepatitis B surface Ag (HBsAg):anti-HBsAg immune complexes were prepared in vitro using Ag radiolabeled with 123I, and injected intravenously. Dynamic and static gamma-scintigraphy was performed to delineate the sites and kinetics of complex clearance. The patient was initially studied when her C2 level and CH50 were zero, and again 1 wk later after treatment with 12 units of FFP, which normalized these parameters. Before treatment there was rapid uptake of complexes by the liver (t90% [time for 90% uptake] = 13.6 min) and rapid clearance from the circulation (t1/2 = 6.8 min). No splenic uptake was detected, and there was no binding of complexes to erythrocyte CR1. Between 30 and 60 min there was release of 11% of the tracer from the liver. In the second study, performed after normalization of classical pathway complement activity, the t1/2 of IC clearance increased to 9.8 min, and t90% was 27 min. Twenty percent of injected complexes now localized to the spleen, and there was no longer any release of complexes between 30 and 60 min. The kinetics of IC processing and the sites of uptake in this posttherapy study were closely similar to two normal subjects studied in parallel, with a maximum of 72% of injected complexes binding to erythrocytes. These observations indicate that the uptake of immune complexes in the spleen in humans is complement-dependent, and suggest that the observed predisposition to SLE in patients with complement deficiency may be related to abnormal processing of immune complexes.
Department of Medicine, Hammersmith Hospital, London, United Kingdom.
K A
KA
Davies
K
K
Erlendsson
H L
HL
Beynon
A M
AM
Peters
K
K
Steinsson
H
H
Valdimarsson
M J
MJ
Walport
D000936:Antigen-Antibody Complex / Q000378:metabolism*; D003175:Complement C2 / Q000032:analysis / Q000172:deficiency / Q000276:immunology*; D015941:Complement Hemolytic Activity Assay; D003171:Complement Pathway, Classical; D005260:Female; D006510:Hepatitis B Antibodies / Q000276:immunology; D006514:Hepatitis B Surface Antigens / Q000276:immunology; D006801:Humans; D008099:Liver / Q000276:immunology; D008297:Male; D010949:Plasma / Q000276:immunology; D017463:Receptors, Complement 3b / Q000032:analysis; D013154:Spleen / Q000276:immunology*; D013667:Technetium
D000936:Antigen-Antibody Complex; D003175:Complement C2; D006510:Hepatitis B Antibodies; D006514:Hepatitis B Surface Antigens; D017463:Receptors, Complement 3b; D013667:Technetium