Inventors:
Elizabeth A. Leadbetter - Roslindale MA, US
Ian R. Rifkin - Boston MA, US
Mark J. Shlomchik - Woodbridge CT, US
Assignee:
Trustees of Boston University - Boston MA
Yale University - New Haven CT
International Classification:
A61K 39/395, A61K 31/7088, A61K 38/16, G01N 33/53, A61P 37/06
US Classification:
4241351, 514 44 A, 514 12, 435 71, 435 724
Abstract:
The present invention provides methods and compositions for treating immune complex associated diseases (ICAD), such as SLE, rheumatoid arthritis, and hepatitis-C related immune complex disease (e.g., cryoglobulinemia) in a subject having an ICAD or at risk for developing ICAD. The invention is based upon the surprising finding that chromatin-containing immune complexes activate autoreactive B cells and dendritic cells by a dual receptor engagement process which, in both cell types, involves a Toll-like receptor (TLR). The methods of treating ICAD comprise administering a compound to an individual in need thereof that either 1) inhibits formation of the immune complex either by preventing formation and/or binding to the TLR, or 2) interferes with binding of an autoantigen-containing immune complex (or the antigenic component thereof) to the TLR, or 3) inhibits signaling pathways initiated by dual engagement of BCR and TLR (in B cells) or FcR and TLR (in dendritic cells) via immune complexed or uncomplexed autoantigens.