Antigen-based heteropolymers facilitate, via primate erythrocyte complement receptor type 1, rapid erythrocyte binding of an autoantibody and its clearance from the circulation in rhesus monkeys.
We investigated the feasibility of using the primate E complement receptor (CR1), in concert with Ag-based heteropolymers (AHP), as a potential therapy to remove autoantibodies from the circulation. AHP are prepared by cross-linking an anti-CR1 mAb with the acetylcholine receptor (AChR), the principal target Ag in myasthenia gravis. In vitro studies demonstrate that this methodology facilitates specific, rapid, and quantitative binding of an anti-AChR mAb to primate Es. In vivo experiments in rhesus monkeys indicate that AHP-mediated binding of an anti-AChR mAb to Es leads to the clearance of the mAb from the circulation. Once bound to the E via the AHP, the autoantibody is transported to the liver and spleen, where it is degraded without destruction of the E. It is therefore likely that the complexes of AHP and target mAb, when bound to Es, are recognized in vivo and processed by a mechanism quite similar to that which occurs when complement-opsonized immune complexes, bound to primate Es, are cleared from the circulation. It may be possible to extend and generalize this work to allow for the development of a simple, noninvasive therapy that can be made specific for the treatment of several different autoimmune diseases.
Ferguson
P J
PJ
Department of Pediatrics, University of Virginia School of Medicine, Charlottesville 22908, USA.
Martin
E N
EN
Greene
K L
KL
Kuhn
S
S
Cafiso
D S
DS
Addona
G
G
Taylor
R P
RP
D000818:Animals; D000911:Antibodies, Monoclonal / Q000276:immunology; D000941:Antigens / Q000032:analysis; D001323:Autoantibodies / Q000378:metabolism*; D001704:Biopolymers / Q000737:chemistry / Q000276:immunology / Q000502:physiology*; D001775:Blood Circulation / Q000276:immunology; D004912:Erythrocytes / Q000737:chemistry* / Q000378:metabolism* / Q000502:physiology; D008253:Macaca mulatta / Q000097:blood*; D011485:Protein Binding / Q000502:physiology; D011950:Receptors, Cholinergic / Q000276:immunology; D011951:Receptors, Complement / Q000032:analysis* / Q000502:physiology*
D000911:Antibodies, Monoclonal; D000941:Antigens; D001323:Autoantibodies; D001704:Biopolymers; D011950:Receptors, Cholinergic; D011951:Receptors, Complement