Okay, so we know that antinuclear antibodies are seen in many different autoimmune diseases (including lupus).But how do you make antibodies against something (a nuclues) that is not “visible” to the immune system? And once you’ve made the antibodies, how do they cause problems?

How are these antibodies made?
It turns out that ultraviolet radiation (the sun) and other environmental insults lead to the apoptosis (programmed death) of cells. As these cells die off, they bust open and their nuclei are exposed. If you don’t completely clear away the dead cells, the nuclei will sit around for a while. In lupus, there is an abnormality in the process of self-tolerance (where the immune system learns to recognize the body’s own antigens, and any immune cells that react against self are deleted). So patients with lupus can (and do) make antibodies against these cell nuclei.

Complexes of the nuclear antigens and antinuclear antibodies are formed. These complexes bind to Fc receptors on B cells and dendritic cells, further stimulating B cells to make autoantibodies as well as immune-system-enhancing cytokines (which can cause more apoptosis). So it’s a nasty self-perpetuating cycle; once you get going, it’s hard to turn off the cycle.

How do the antibodies cause problems?
Most of the organ-based symptoms in lupus (like kidney disease and skin disease) are caused by immune complexes. Anti-DNA antinuclear antibodies are virtually diagnostic of lupus; you can find DNA-antiDNA complexes all over in patients with lupus. It’s not a good idea to have these immune complexes around, because they can stick to endothelial cells in vessels, where they call in inflammatory cells and complement, both of which are damaging to the vessel wall. This process is called a type III hypersensitivity reaction – and it happens in lots of other diseases besides lupus too.

Sometimes, you can see evidence of the antinuclear antibodies in tissues. Antinuclear antibodies will bind to any damaged cells within a particular organ or tissue, causing the chromatin to become more smooth-looking. You can see these weird-looking nuclei (called LE, or lupus erythematosus, bodies) under the microscope. Sometimes, you can even see phagocytic cells (neutrophils or macrophages) eating up these denatured nuclei. These dead-nucleus-containing phagocytes are called LE cells, and you can see one in the image above (the dead nucleus is the curvy, bland-looking one on the right). In fact, in the olden days, the lab would take a tube of blood and shake it up (to disrupt the cells, expose the nuclei, and allow the patient’s antinuclear antibodies to bind) as a test for lupus! If you saw LE cells, that would be indicative of lupus.