Antigen-based heteropolymers. A potential therapy for binding and clearing autoantibodies via erythrocyte CR1

Arthritis Rheum. 1995 Feb;38(2):190-200. doi: 10.1002/art.1780380207.

Abstract

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.

Conclusion: This methodology may allow for development of a new therapy to facilitate autoantibody clearance in autoimmune disease.

Publication types

  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • Animals
  • Antibodies, Antinuclear / blood
  • Antibodies, Monoclonal / therapeutic use
  • Antigens / analysis*
  • Autoantibodies / metabolism
  • Binding Sites, Antibody
  • Chromium Radioisotopes
  • Enzyme-Linked Immunosorbent Assay
  • Erythrocytes / chemistry
  • Erythrocytes / immunology
  • Erythrocytes / metabolism
  • Humans
  • Immunoglobulin G / immunology
  • Iodine Radioisotopes
  • Macaca mulatta
  • Polymers / chemistry
  • Receptors, Complement 3b / immunology*

Substances

  • Antibodies, Antinuclear
  • Antibodies, Monoclonal
  • Antigens
  • Autoantibodies
  • Chromium Radioisotopes
  • Immunoglobulin G
  • Iodine Radioisotopes
  • Polymers
  • Receptors, Complement 3b