Moving towards a cure: blocking pathogenic antibodies in systemic lupus erythematosus

• Published in: Journal of internal medicine 2011-01, Vol.269 (1), p.36-44
• Main Authors: Diamond, B., Bloom, O., Al Abed, Y., Kowal, C., Huerta, P. T., Volpe, B. T.
• Format: Article
• Language: English
• Subjects: Animals; Antibodies, Antinuclear - therapeutic use; autoantibodies; Autoantibodies - immunology; Autoimmune Diseases - immunology; Autoimmune Diseases - therapy; Biological and medical sciences; Disease Models, Animal; DNA - immunology; General aspects; Humans; Lupus Erythematosus, Systemic - immunology; Lupus Erythematosus, Systemic - therapy; Lupus Vasculitis, Central Nervous System - immunology; Medical sciences; Mice; Receptors, N-Methyl-D-Aspartate - immunology; Sarcoidosis. Granulomatous diseases of unproved etiology. Connective tissue diseases. Elastic tissue diseases. Vasculitis; systemic lupus erythematosus; therapeutic strategy
• ISSN: 0954-6820; 1365-2796
• DOI: 10.1111/j.1365-2796.2010.02318.x

Diamond B, Bloom O, Al Abed Y, Kowal C, Huerta PT, Volpe BT (Autoimmune & Musculoskeletal Disease Center, The Feinstein Institute for Medical Research, Manhasset; and Department of Neurology & Neuroscience, Burke Cornell Medical Research Institute, Weill Medical College of Cornell University, White Plains, NY, USA) Moving towards a cure: blocking pathogenic antibodies in systemic lupus erythematosus (Key Symposium). J Intern Med 2011; 269: 36–44. .  Systemic lupus erythematosus (SLE) is characterized by the presence of autoantibodies that can mediate tissue damage in multiple organs. The underlying aetiology of SLE autoantibodies remains unknown, and treatments aimed at eliminating B cells, or limiting their function, have demonstrated limited therapeutic benefit. Thus, the current therapies for SLE are based on the concept of nonspecific immunosuppression and consist of nonsteroidal anti‐inflammatory drugs (NSAIDS), corticosteroids, anti‐malarials and cytotoxic drugs, all of which have serious adverse side effects including organ damage. The major auto‐specificity in SLE is double‐stranded (ds) DNA. Many anti‐dsDNA antibodies cross‐react with non‐DNA antigens that may be the direct targets for their pathogenic activity. Studying anti‐dsDNA antibodies present in SLE patients and in animal models of lupus, we have identified a subset of anti‐dsDNA antibodies which is pathogenic in the brain as well as in the kidney. We have recently demonstrated that specific peptides, or small molecules, can protect target organs from antibody‐mediated damage. Thus, it might be possible to treat the aspects of autoimmune disease without inducing major immunosuppression and ensuing infectious complications.