Rapid clearance of the lupus antigen Sm is delayed by autoantibody: a possible mechanism of autoimmunity perpetuation.
Sm ribonucleoprotein complex was immunopurified and labelled with 125I. After i.v. injection into normal mice 125I-Sm was cleared with a half life of less than 3 min, mainly to the liver (54% at 15 min). With time there was a progressive reduction in liver uptake (13.3% at 1 h), and this was associated with the appearance of increasing amounts of trichloroacetic acid soluble 125I in serum, suggesting complete Sm catabolism. Injection of 125I-Sm as a preformed immune complex with human anti-Sm antibody was associated with slower antigen removal from the circulation (half life 15 min), more gradual liver uptake (27% at 1 hr), and less degradation products in the serum than after injection of antigen alone. These data suggest that release of 125I-Sm into the circulation is followed by specific organ uptake and antigen degradation. In the form of an immune complex, the rapid removal mechanism is impaired, and antigen persists in the circulation in an undegraded form. Simultaneous production of anti-Sm antibody and Sm antigen release following tissue destruction could lead to amplification of any primed immune response as a result of autoantigen drive in systemic lupus erythematosus.
Field
M
M
Clinical Immunology Division, Kennedy Institute of Rheumatology, London, England.
Melsom
R D
RD
Brennan
F M
FM
Williams
D G
DG
Schreiber
L
L
McCarthy
D A
DA
Maini
R N
RN
Nelsom
R D
RD
D000818:Animals; D000936:Antigen-Antibody Complex / Q000276:immunology*; D001323:Autoantibodies / Q000276:immunology*; D001324:Autoantigens / Q000493:pharmacokinetics*; D006207:Half-Life; D008657:Metabolic Clearance Rate; D051379:Mice; D008807:Mice, Inbred BALB C; D012261:Ribonucleoproteins / Q000493:pharmacokinetics*; D017411:Ribonucleoproteins, Small Nuclear; D055517:snRNP Core Proteins
D000936:Antigen-Antibody Complex; D001323:Autoantibodies; D001324:Autoantigens; D012261:Ribonucleoproteins; D017411:Ribonucleoproteins, Small Nuclear; D055517:snRNP Core Proteins