A study in the May 2007 issue of Nature Immunology may shed light on the cause of immune activation associated with systemic lupus erythematosus (SLE) -- the second most common autoimmune disease in humans.
Found more often in women than in men, SLE is associated with the abnormal production of antibodies that 'attack' normal molecules in the body, including a person's own DNA. As a result, debilitating inflammation, including skin rashes, hypertension, arthritis, and kidney and nervous system problems, ensues. Anthony Coyle and colleagues studied a protein called HMGB1 that normally binds to DNA in the cell nucleus. HMGB1 is also found in blood plasma, where it can bind to DNA released from dying cells. In many SLE patients, such DNA is also often the target of 'abnormal' lupus antibodies. As a result, antibody-HMGB1-DNA protein complexes form. The new study by Coyle and colleagues finds that antibody-HMGB1-DNA complexes in blood plasma from SLE patients can stimulate immune cells to produce potent inflammatory proteins associated with autoimmunity.By demonstrating a role for HMGB1 in SLE inflammation, Coyle and colleagues provide unique insight into the pathogenesis associated with increasingly prevalent autoimmune diseases such as SLE. However, whether blocking the inflammatory function of HMGB1 will help SLE patients remains a question for future investigation.
Author contact:
Anthony J. Coyle (MedImmune, Inc, Gaithersberg, MD, USA)
E-mail: coylea@medimmune.com
Abstract available online.