The LE cell: crime scene or crime stopper?

have often said that the lupus erythematosus (LE) cell is the most important cell in all of medicine. Th is judgment does not refl ect the cell's putative function in auto-immunity but rather the insights it has provided into the mechanisms of autoimmunity. Discovered fortuitously by Hargraves and colleagues (see Suggested reading below) at the Mayo Clinic, the test to detect this cell is very simple. A sample of peripheral blood is disrupted, incu-bated, and then spread onto a slide for inspection, after Wright's staining, under an old-fashioned light microscope. If the patient has lupus, then, voilà, the LE cell stands out among the mundane and ordinary red and white cells that populate the blood. No doubt, my view of the signifi cance of the LE cell is parochial and relates to my identity as a rheumatologist who has spent a career trying to solve the enigmas of anti-DNA antibodies. Th e competition for the LE cell is also not that stiff. 'Tart' cells are now forgotten and the Reed-Sternberg cell, though valuable for the diagnosis of Hodgkin's disease, has a very confusing phenotype, representing a B cell of some kind. Truly, what has the Reed-Sternberg cell revealed about the basis of malig-nancy? In contrast, the study of the LE cell has been a bonanza for autoimmunity. As is now recognized, the LE cell phenomenon involves, in the presence of anti-nuclear antibodies (ANAs) and complement, the phagocytosis of a cell nucleus. In peripheral blood, the cell doing the engulfi ng is likely a neutrophil. For many years, the focus on the LE cell phenomenon was the ANA component and specifi cities that can bind nuclear molecules; this focus spawned simpler and more widely used tests such as the fl uorescence anti-nuclear antibody (FANA) test. Other elements of the LE cell phenomenon raise salient issues that remain prime topics for investigation: the role of complement in the binding and clearance of nuclear material; the activation of neutrophils by nuclear molecules; and, perhaps most important, the existence of nuclear material outside cells. Of events key to the creation of an LE cell, the translocation of an intact nucleus from the inside to the outside of a cell is perhaps the most mysterious and, for many years, attracted little investigative interest. Physiological enucleation is thought to occur essentially only in the bone marrow during red cell development and in the eye during the …