image: Upon inflammation, a transcription factor (NF-kB) activates the translation of a firefly protein (Luciferase) generating photons in cells of diseased tissues. The technique is highly sensitive and predicts development, severity and outcome of disease. Top: Skin disease with gradual involvement of ears and snout. Middle: Arthritis development, light signals appear several weeks before clinical signs. Bottom: Development of inflammatory signals from the intestines (inflammatory bowel disease, and perianal inflammation). view more
Credit: Zangani et al, Am J Pathol, 2009
Oslo, Norway MA — Current research describes a new method to track the development of autoimmune diseases before the onset of symptoms. The related report by Zangani et al, "Tracking early autoimmune disease by bioluminescent imaging of NF-κB activation reveals pathology in multiple organ systems," appears in the April 2009 issue of The American Journal of Pathology.
Autoimmune diseases such as lupus, multiple sclerosis, rheumatoid arthritis and diabetes are caused when the immune system attacks the body's own cells. Normally, immune cells are prevented from attacking normal cells; however, in patients with autoimmune disease, this "tolerance" is lost. The immediate causes of autoimmune diseases remain unknown, partially due to the inability to detect disease before the onset of symptoms. Early detection of autoimmune disease is critical for assessing new treatments.
The molecule NF-κB is activated by inflammation, which plays a key role in autoimmune disease development, making NF-κB a prime candidate to track autoimmune activity. Researchers at the University of Oslo led by Drs. Ludvig Munthe and Bjarne Bogen in collaboration with Rune Blomhoff engineered NF-κB such that it would emit light when activated. Using a mouse model of systemic autoimmunity with features of lupus, they found that NF-κB activation signals were present in affected organs several weeks before the clinical manifestations of disease. The light signal intensity correlated with disease progression. NF-κB tracking may therefore provide a new tool in the evaluation of early autoimmune therapies.
The article from Zangani et al "indicate[s] that NF-κB mediated bioluminescence is a very sensitive and early indicator of inflammation and disease", allowing precise identification of incipient disease sites for biomedical and pathogenetic studies. In future studies, Drs. Munthe, Bogen, and colleagues will utilize this new model "for studies on early intervention, e.g. drug treatment, to prevent or treat autoimmune disease", and for studies of the development of B cell lymphoma.
The Norwegian Research Council, The University of Oslo, Medinnova and Rikshospitalet Medical Center funded the work.
Zangani M, Carlsen H, Kielland A, Os A, Hauglin Harald, Blomhoff Rune, Munthe L A, Bogen B: Tracking early autoimmune disease by bioluminescent imaging of NF-κB activation reveal pathology in multiple organ systems. Am J Pathol 2009 174: 1358-1367
For press copies of the articles, please contact Dr. Angela Colmone at 301-634-7953 or acolmone@asip.org.
For more information on Drs. Munthe and Bogen, please contact: Gina Scholz, Public Relations and Communications Department, Rikshospitalet, Oslo University Hospital, N0147, Oslo Norway, Tel +47 2307 1231, cell phone +47 9524 8688, email Gina.Scholz@rikshospitalet.no or contact the authors by e-mail: l.a.munthe@medisin.uio.no, b.bogen@medisin.uio.no.
The American Journal of Pathology, official journal of the American Society for Investigative Pathology, seeks to publish high-quality, original papers on the cellular and molecular biology of disease. The editors accept manuscripts that advance basic and translational knowledge of the pathogenesis, classification, diagnosis, and mechanisms of disease, without preference for a specific analytic method. High priority is given to studies on human disease and relevant experimental models using cellular, molecular, animal, biological, chemical, and immunological approaches in conjunction with morphology.
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American Journal Of Pathology