HMGB1: a smoking gun in lupus nephritis?

High-mobility group box 1 protein (HMGB1) is a prototypic alarmin that is released from activated and dying cells. Because of its proinflammatory activities, HMGB1 could mediate key events in the pathogenesis of systemic lupus erythematosus, a possibility supported by elevations of HMGB1 in patient blood and increased expression in renal biopsies. The biology of HMGB1 is complicated, however, and its activity is dependent on redox state as well as binding to other molecules such as cytokines. Defining more precisely the role of HMGB1 in lupus will require treatment studies to block the activity of this alarmin in animal models and ultimately patients.