%0 Journal Article
%T HMGB1: a smoking gun in lupus nephritis?
%A David S Pisetsky
%J Arthritis Research & Therapy
%D 2012
%I BioMed Central
%R 10.1186/ar3754
%X A smoking gun is probably the most dramatic and iconic evidence of a crime. The concept of the smoking gun originated in a Sherlock Holmes story and then languished until it exploded into awareness during the impeachment hearings of Richard Nixon. As now understood, a smoking gun is an incontrovertible piece of evidence to establish a crime and even identify the perpetrator. This is especially true if the gun, sulfurous fumes streaming from the barrel, resides in the hand of a suspect, the murder victim bleeding nearby.In rheumatology as in all of medicine, investigators are forever searching for the smoking guns of pathogenesis. The identification of such guns, especially when found at the crime scene (such as a kidney biopsy), can delineate the mechanism of tissue injury as well as suggest new targets of therapy. Smoking guns in medicine can be very elusive, however, and cold cases abound. Assembling a case beyond a reasonable doubt can require a multitude of in vitro and in vivo studies, including treatment trials in animal models as well as patients.In the previous issue of Arthritis Research & Therapy, Zickert and colleagues [1] provided important new evidence implicating high-mobility group box 1 protein (HMGB1) as a mediator of lupus nephritis, and the enhanced expression of HMGB1 is perhaps a smoking gun in the pathogenesis of a very complicated disease. As the data presented indicate, levels of HMGB1 are elevated in the blood of patients with lupus nephritis; furthermore, renal biopsies showed increased HMGB1 expression in the mesangium and endothelium. The elevations of HMGB1 in blood occurred in patients with different histopathological forms of lupus nephritis but, interestingly, did not vary much over time or with treatment [1].These observations are important in view of the biological properties of HMGB1. HMGB1 is a prototype alarmin and, indeed, the prime example of this class of immune mediator. In other terminology, HMGB1 is a DAMP (damage-associate
%U http://arthritis-research.com/content/14/2/112