May is Lupus awareness month and May 10th is World Lupus Day, therefore I would like to use this blog post to discuss a slightly different aspect of antibodies. So far we have considered the functionality of antibodies as part of the host defense mechanism; as well as their utility in research, diagnostics, and as therapeutics. However, antibodies can also participate in disease pathology and most notably in autoimmune diseases. Autoimmune diseases occur when the immune system attacks self and generates a chronic inflammatory condition that leads to tissue damage. Lupus is one such disease.
What is Lupus?
Lupus is a chronic inflammatory disease caused by the immune system attacking the cells, tissues, and organs of the host. Lupus can attack nearly all tissues and organs and typically multiple organs are simultaneously impacted. The symptoms range from mild to life threatening and according to The Lupus Foundation of America it is estimated that there are 1.5 million Americans diagnosed with Lupus and at least 5 million worldwide. Women make up 90% of Lupus patients and women of color are more likely to get Lupus.
While the specific cause of Lupus is unknown it is understood that genetics, gender, and the environment all play a role. Diagnosis can be difficult as symptoms flare, and are not always present at the same time, in addition many of the symptoms mimic other conditions and need to be ruled out prior to a positive Lupus diagnosis. As there is no single diagnostic marker that identifies Lupus, it often takes years to accurately diagnose.
One of the characteristic features of the development and progression of Lupus is the production of autoantibodies, or antibodies that recognize self antigens. As we have discussed in prior blog articles, antibodies help mediate the detection, capture, and removal of bacteria, viruses, and other infectious pathogens. In autoimmune diseases such as Lupus that generate autoantibodies, the self antigens become the target of the immune system attack and therefore causes damage to one’s own tissues. The development of autoantibodies is a result of what is referred to as “breaking tolerance”. During the development of B cells and T cells, populations of harmful autoreactive B- and T-cells are removed to generate tolerance (of self); however in an autoimmune disease these harmful lymphocytes escape tolerance, become activated and trigger inflammation and tissue damage.
Lupus has several characteristic autoantibody profiles and is often used in the diagnostic process. The genetic analysis of autoantibodies has led to insights that have advanced our understanding of antibodies in general. For example, Dr. Martin Weigert discovered and defined mechanisms of light chain editing and immunoglobulin diversity that not only provided insight into autoantibodies and autoimmunity but also advanced our overall knowledge of host defense.
New Therapies & New Discoveries
Unfortunately there is no cure for Lupus. Until recently, the only treatments were immune suppressants and chemotherapeutics to reduce the immune system’s attack, treatment of inflammation with NSAIDs and corticosteroids, antimalarials for treating autoantibody production and sun sensitivity, and others for the various clinical symptoms. Recently the first drug developed specifically for Lupus was approved. Benlysta is an antibody therapy that specifically targets B cells to interrupt autoantibody production.
Recent discoveries have identified possible triggers as well as new methods for treating individual Lupus patients. While much is left to learn, a great deal of progress has been made in understanding the development of Lupus which will ultimately lead to better diagnostics and promising treatments. To this end, a new large scale research program, known as the Accelerated Medicines Partnership, has been established by the National Institute’s of Health specifically to tackle the complexity of autoimmunity, including Lupus.
Prior to my joining BBI, I spent over 25 years researching Lupus and in particular the development of autoantibodies. Lupus can be a debilitating and disruptive disease that has significant emotional, physical, and economic impacts to patients and their families. For more information on Lupus I have compiled a list of a few organizations that are dedicated to Lupus education and research:
BBI is pleased to make a donation to the Lupus Research Institute in honor of World Lupus Day.