OBJECTIVE: Synthetic oligodeoxynucleotides (ODN) expressing TTAGGG motifs suppress the production of proinflammatory cytokines and have been proven effective at blocking the development of certain organ-specific autoimmune diseases. We undertook this study to determine whether suppressive ODN alter the development of systemic autoimmunity, by evaluating their effect on the progression of lupus-like disease in NZB x NZW (NZB/NZW) mice. METHODS: We repeatedly treated mice with suppressive ODN before or after the onset of proteinuria. We monitored the effect of treatment on the onset, severity, and immunologic correlates of disease. RESULTS: Treatment with suppressive ODN significantly prolonged lifespan while delaying the onset and progression of glomerulonephritis in NZB/NZW mice. Clinical improvement was accompanied by a significant reduction in anti-double-stranded DNA autoantibody production and by significantly reduced secretion of interferon-gamma and interleukin-12 in vivo. CONCLUSION: Suppressive ODN may be of benefit in the treatment of chronic systemic autoimmune diseases such as systemic lupus erythematosus.
OBJECTIVE: Synthetic oligodeoxynucleotides (ODN) expressing TTAGGG motifs suppress the production of proinflammatory cytokines and have been proven effective at blocking the development of certain organ-specific autoimmune diseases. We undertook this study to determine whether suppressive ODN alter the development of systemic autoimmunity, by evaluating their effect on the progression of lupus-like disease in NZB x NZW (NZB/NZW) mice. METHODS: We repeatedly treated mice with suppressive ODN before or after the onset of proteinuria. We monitored the effect of treatment on the onset, severity, and immunologic correlates of disease. RESULTS: Treatment with suppressive ODN significantly prolonged lifespan while delaying the onset and progression of glomerulonephritis in NZB/NZW mice. Clinical improvement was accompanied by a significant reduction in anti-double-stranded DNA autoantibody production and by significantly reduced secretion of interferon-gamma and interleukin-12 in vivo. CONCLUSION: Suppressive ODN may be of benefit in the treatment of chronic systemic autoimmune diseases such as systemic lupus erythematosus.
Authors: Uma Sriram; Linda Varghese; Heather L Bennett; Neelakshi R Jog; Debra K Shivers; Yue Ning; Edward M Behrens; Roberto Caricchio; Stefania Gallucci Journal: J Immunol Date: 2012-06-01 Impact factor: 5.422
Authors: Jia Qi; Krisztina Buzas; Huiting Fan; Jeffrey I Cohen; Kening Wang; Erik Mont; Dennis Klinman; Joost J Oppenheim; O M Zack Howard Journal: J Immunol Date: 2011-04-22 Impact factor: 5.422
Authors: Deborah L Hodge; Cyril Berthet; Vincenzo Coppola; Wolfgang Kastenmüller; Matthew D Buschman; Paul M Schaughency; Hidekazu Shirota; Anthony J Scarzello; Jeff J Subleski; Miriam R Anver; John R Ortaldo; Fanching Lin; Della A Reynolds; Michael E Sanford; Philipp Kaldis; Lino Tessarollo; Dennis M Klinman; Howard A Young Journal: J Autoimmun Date: 2014-02-28 Impact factor: 7.094