The Scientific Revolution Behind Lupus Research

Lupus research has gone a long way since its original designation as a mere skin disease these days, we know it is a chronic autoimmune disorder that can involve much more than just your skin. But what advancements allowed us to recognize the complicated nature of lupus? This article will highlight the revolutionary discoveries during the twentieth century that led to a more detailed diagnosis and treatment of lupus.

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Cases of lupus can be traced all the way back to Hippocrates' time in 460-375 BC. However, the systemic form of lupus wouldn’t be formally established until 1904 after extensive work from Jadassohn and Sir William Osler:

• Jadassohn published extensive reviews of Discoid and Systemic Lupus Erythematosus (SLE), highlighting the clinical features and pathologic findings.

• Osler published an astounding 29 cases of “erythema group of diseases,” and though only two in those cases genuinely described SLE, he still contributed to the medical field’s greater understanding of how skin diseases could be accompanied by various systemic manifestations.

Both Jadassohn and Sir William Osler would lay the groundwork for future immunology breakthroughs by understanding lupus as more than just a skin affliction. Breakthroughs such as:

• The discovery of the LE cell by Hargraves and Colleagues in 1948: Hargraves observed a phagocytic phenomenon in the bone marrow of lupus patients in which white blood cells called neutrophils would consume the nuclear material released from the abundance of cells that died from lupus autoantibodies. These cells were termed lupus erythematosus cells or simply LE cells. The presence of LE cells was subsequently considered a biomark of lupus, trailblazing a way for the future application of immunology to lupus studies and the more efficient diagnosing of milder forms of lupus. Testing for LE cells is still factored into lupus diagnosis today, though its become somewhat obsolete due to modern methods of diagnosis.

• The discovery of lupus-related autoantibodies throughout the 1950s: Syphilis testing done by Moore would find that lupus patients produced specific autoantibodies that would mistakenly flag them as positive during testing. In fact, he found that 7% of the 148 individuals who had chronic false-positive syphilis tests had developed systemic lupus, and 30% had symptoms consistent with collagen disease, where those autoantibodies were still produced. Furthermore, Friou would apply a microscopy technique called immunofluorescence to demonstrate the presence of antinuclear antibodies—autoantibodies that specifically target the cell’s nucleus—in lupus patients’ blood. Both these studies would be revolutionary in tracing the development of SLE and its treatments.

Several therapies would not be possible today if not for the brilliant discoveries of scientists and doctors dedicated to lupus treatment. The first medication used for lupus was an antimalarial named quinine in 1894, but treatment really began to change in the mid-twentieth century. For example, your doctor may prescribe you corticosteroids in order to help your lupus, and we can thank Kendall and Hench in 1952 for being the first to introduce such therapies into lupus treatment.

Following Kendall and Hench would be other immunosuppressants which researchers already had a model of from organ transplants that required a suppression of immune responses and attendant inflammation. Thus, the late twentieth century brought about Azathioprine and Cytoxan. Cytoxan was particularly groundbreaking, as it was able to prevent mortality to life-threatening manifestations of lupus and kidney failure. Austin and colleagues found that when it came to cases of lupus nephritis, pairing Cytoxan with another immunosuppressant called prednisone was superior to just prednisone alone.

Lupus has been documented for a long time now, but the groundwork of lupus treatment and diagnosis has been particularly built on the studies of researchers within the twentieth century, such as Jadassohn, Osler, Hargraves and colleagues, Moore, Friou, Kendall and Hench, and Austin and colleagues. The truly remarkable research done in the past inspires hope for what’s to come in the twenty-first century and beyond.

The history of lupus erythematosus. From Hippocrates to Osler | National Library of Medicine

The History of Lupus | Lupus Foundation of America

Anti-Nuclear Antibodies | Encyclopedia of Immunology (Second Edition)

An introduction to Performing Immunofluorescence Staining | NIH

History of Lupus | Columbia University Irving Medical Center