Antigen-based heteropolymers. A potential therapy for binding and clearing autoantibodies via erythrocyte CR1.
OBJECTIVE
To determine if complexes containing monoclonal antibodies to CR1 cross-linked with antigen (antigen-based heteropolymers [AHP]) can bind the corresponding autoantibody to primate erythrocyte CR1 and promote autoantibody clearance from the circulation.


METHODS
AHP were constructed by cross-linking double-stranded DNA (dsDNA) to monoclonal antibodies to CR1. The ability of AHP to facilitate binding of human anti-dsDNA antibodies to primate erythrocytes was studied in vitro using a variety of radioimmunoassays (including Farr assays), enzyme immunoassays, and fluorescence-activated cell sorting. In addition, we used a monkey model to study in vivo the AHP-mediated clearance of passively infused human anti-dsDNA antibodies.


RESULTS
Large amounts of lupus IgG anti-dsDNA antibodies can be specifically bound to human erythrocytes via the complexes, and studies in 2 rhesus monkeys indicate that the erythrocyte-bound antibodies are rapidly cleared from the circulation.


CONCLUSIONS
This methodology may allow for development of a new therapy to facilitate autoantibody clearance in autoimmune disease.
University of Virginia School of Medicine, Charlottesville 22908.
P J
PJ
Ferguson
C J
CJ
Reist
E N
EN
Martin
C
C
Johnson
K L
KL
Greene
S
S
Kuhn
J
J
Niebur
W
W
Emlen
R P
RP
Taylor
D000818:Animals; D000974:Antibodies, Antinuclear / Q000097:blood; D000911:Antibodies, Monoclonal / Q000627:therapeutic use; D000941:Antigens / Q000032:analysis*; D001323:Autoantibodies / Q000378:metabolism; D001666:Binding Sites, Antibody; D002860:Chromium Radioisotopes; D004797:Enzyme-Linked Immunosorbent Assay; D004912:Erythrocytes / Q000737:chemistry / Q000276:immunology / Q000378:metabolism; D006801:Humans; D007074:Immunoglobulin G / Q000276:immunology; D007457:Iodine Radioisotopes; D008253:Macaca mulatta; D011108:Polymers / Q000737:chemistry; D017463:Receptors, Complement 3b / Q000276:immunology*
D000974:Antibodies, Antinuclear; D000911:Antibodies, Monoclonal; D000941:Antigens; D001323:Autoantibodies; D002860:Chromium Radioisotopes; D007074:Immunoglobulin G; D007457:Iodine Radioisotopes; D011108:Polymers; D017463:Receptors, Complement 3b