Rheumatoid Arthritis and Systemic Lupus Erythematosus As Immune Complex Diseases‪.‬

Rheumatology came late to the game of medical science and even later to immunology. From 1933 to 1948, our medical specialty was a descriptive art-we had no idea, in any meaningful way, what was going on. Cardiologists had their EKGs and digitalis, the endocrinologists had their thyroid tests and extracts, but rheumatologists seemed condemned to stand idly by to watch their patients turn into cripples or die in lupus crisis after one or another stopgap treatments. Oh yes, we had diathermy, gold salts, paraffin injections and, believe it or not, bee venom. We knew how to treat gout with colchicine, were just learning to give penicillin to prevent rheumatic fever, but by and large our treatment of joint disease or even systemic lupus erythematosus (SLE) was limited to aspirin, aspirin, and more aspirin. All that changed in the annus mirabilis of our field, 1948. At a staff meeting of the Mayo Clinic in January of 1948, Malcolm M. Hargraves described a strange kind of cell that formed in blood samples of patients with SLE.1 Before 1950, we could not really tell who had SLE and who did not; we had "no clue" as to why SLE was so often fatal. Hargraves had discovered what he called the "LE cell," which finally permitted us not only to make a diagnosis of the disease, but also told us what was going wrong with these poor women. The LE cell, it turned out over the years, is a white blood cell (a neutrophil) that has ingested the dying nucleus of another cell, against which lupus patients make antibodies. Complement was involved, acting as an opsonin. It also turned out that those antibodies against the nucleus and/or its constituents--the anti-DNA antibodies--were just the tip of an iceberg. SLE patients produce a dazzling number of antibodies, with their Fab regions directed against bits and pieces of their own cells. Their immune system recognizes such bits of "self" as if they were a microbe, a tad of "non-self that wants expunging. Hargrave's discovery of the LE cell sparked the study of autoimmunity and lifted rheumatology over the threshold of science. (1)