Evaluation of Antigen-Based Heteropolymer for Treatment of Systemic Lupus Erythematosus in a Nonhuman Primate Model
Autor: | Josaih Adaelu, Rose Ebelle, Nadya Lukacher, Steven E. Pincus, Xun Chen, James P. Porter, Roger Zabinski, Linda L. Nardone, Lisa Duncan, Wu Peng, Muctarr Sesay, George L. Spitalny, Juan Li, Nehal Mohamed, Leslie S. Casey |
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Rok vydání: | 2002 |
Předmět: |
Male
Erythrocytes medicine.drug_class Immunology Antibody Affinity Lupus nephritis Complement receptor Monoclonal antibody Antigen Salmon immune system diseases medicine Animals Humans Lupus Erythematosus Systemic Immunology and Allergy Antigens skin and connective tissue diseases Lupus erythematosus biology Autoantibody Antibodies Monoclonal DNA medicine.disease Disease Models Animal Macaca fascicularis Titer Antibodies Antinuclear Receptors Complement 3b biology.protein Female Antibody |
Zdroj: | Clinical Immunology. 105:141-154 |
ISSN: | 1521-6616 |
Popis: | Autoantibodies that react with double-stranded DNA (dsDNA) are a hallmark for diagnosis of systemic lupus erythematosus (SLE) and are also considered the pathogenic subset that is most associated with lupus nephritis. As an agent to remove the pathogenic dsDNA antibodies from the circulation of SLE patients, we are developing an antigen-based heteropolymer (AHP). The AHP consists of a monoclonal antibody to the complement receptor (CR1) cross-linked to salmon testis dsDNA to effect clearance of anti-DNA antibodies by binding them to erythrocyte CR1. Utilizing a cynomolgus monkey model for SLE in which we infused plasma from SLE patients containing a high titer of high-avidity anti-dsDNA antibody, we have evaluated the safety and efficacy of AHP infusion. The results demonstrate that AHP rapidly (within 2 min of infusion) binds to monkey erythrocytes without causing any toxicological effects. We also demonstrate that human Ig (G+M) antibodies are rapidly bound to the AHP-erythrocyte complex. These events are mirrored in their kinetics by a substantial drop in the level of high-avidity dsDNA antibody in the plasma. |
Databáze: | OpenAIRE |
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