Journal
EUROPEAN JOURNAL OF IMMUNOLOGY
Volume 37, Issue 12, Pages 3582-3586Publisher
WILEY-V C H VERLAG GMBH
DOI: 10.1002/eji.200737815
Keywords
F1 mice; lupus; (NZB x NZW); toll-like receptor
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The presence of autoantibodies specific for nucleic acid-associated antigens is the hallmark of systemic lupus erythematosus (SLE). We have recently developed a specific inhibitor of TLR7 and TLR9, called immunoregulatory sequence (IRS) 954, and showed that it inhibits the induction of IFN-alpha by human plasmacytoid dendritic cells in response to DNA and RNA viruses and isolated immune complexes from lupus patients. In this study, we show that IRS 954 can prevent progression of disease when injected in the lupus prone (NZB x NZW)F-1 mice. Following treatment, we observed a significant reduction of serum levels of nucleic acid-specific autoantibodies as well as decreased proteinuria, reduced glomerulonephritis, end-organ damage and increased survival. These data demonstrate that in addition to its ability to block IFN-alpha IRS 954 can reduce symptoms in a lupus model and thus represents a promising therapeutic agent for the treatment of SLE.
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