By Noel R. Rose,M.D.,Ph.D.,Chairperson, AARDA Scientific Advisory Board;Director of Autoimmune Research Center, The Johns Hopkins University, InFocus, Vol.9, No.2, June 2001

Autoimmune disease defined
     The basic definition of an autoimmune disease is a disorder caused by an autoimmune response, i.e., an immune response directed to something in the body of the patient. Since autoimmunity can affect any organ in the body (including brain, skin, kidney, lungs, liver, heart, and thyroid), the clinical expression of the disease depends upon the site affected. In our system of highly compartmentalized medicine, patients with autoimmune disease may be cared for by physicians in virtually any medical specialty.

     For many years, the medical establishment was skeptical of the existence of autoimmunity since it seemed to defy common sense. Why would a person develop an immune response to himself rather than to an invading germ? When we realize that the immune response is a powerful and complex biological reaction, however, we can understand that, on occasion, the reaction can misfire. These misfirings of the immune system are the reason that autoimmune diseases occur. Sometimes autoimmunity can be the initiating cause of the disease. In other cases, autoimmunity can contribute to, or exaggerate, a disease caused by something else. The presence of an autoimmune response is signaled by the appearance of autoantibody in the circulation, and so the demonstration of a particular autoantibody usually constitutes the path to recognize an autoimmune disease.

Multiple causes: genetic

     What could cause the immune system to misfire in such a harmful manner? Part of the answer is genetic. All of the autoimmune diseases show evidence of a genetic predisposition. No single gene by itself causes an autoimmune disease; instead, a coalescence of several genes in certain individuals, in the aggregate, heightens significantly the overall possibility of developing an autoimmune disease. Some of these genes may be specific for a certain disease, but others predispose to autoimmunity in general. That explains why a single patient may have more than one autoimmune disease or why autoimmune diseases are more common in some families than others.

     For the patients, this is an important bit of information because it means that she must alert a physician to the presence of autoimmune disease in the family. We use the pronoun "she" because most autoimmune diseases occur more frequently in women. The reason for this sex-related difference is not known, but it may reflect the involvement of hormones in regulation of the immune response.

Multiple causes: environmental triggers

     Another common characteristic of all the autoimmune diseases in humans is that an outside agent is required to initiate the harmful autoimmune process. These agents are called environmental triggers. Even with a genetic predisposition, most people do not develop an autoimmune disease unless something external acts on their body. Sometimes this may be infection; for example, a well known autoimmune disease, rheumatic fever, is associated with a preceding infection by a streptococcus.

     Another autoimmune disease, lupus, may be precipitated by exposure to sunlight. Sometimes components of the diet may influence the development of disease; for example, in autoimmune diseases of the thyroid, dietary iodine may be an important initiating factor. It must be emphasized, however, that these environmental triggers act only in individuals with a genetic predisposition and not in the population at large. If the environmental agent can be identified and the patient warned to avoid it, the autoimmune disease may never occur, even in the most highly predisposed individual. One important outcome of the human genome project will be the identification of genes that contribute to an unusual autoimmune susceptibility. Individuals with the greatest risk can than be forewarned.

Overlapping diseases

     Thus, it is important, from the clinical point of view, to consider the autoimmune diseases as a united group of disorders. The presence of one autoimmune disease will alert the physician and the patient to the possibility that a second or third autoimmune disease may occur in the same individual or in other members of the same family. The presence of one autoimmune disease may be a sign of heightened susceptibility to a second disease.

Research for new treatments

     A great deal of benefit also arises from considering the autoimmune diseases together in the realm of medical research. Virtually all autoimmune diseases are dependent upon the production of an abnormal population of T cells, one of the circulating white blood cells. An effective treatment of autoimmune disease, more efficacious than anything we now have in our armamentarium, would come from finding ways of identifying and turning off these disease-producing T cells. As modern molecular immunology has taught us, the T cell has a unique surface structure. By use of experimental animals, we are learning to identify these disease-associated structures on T cells and to develop methods to eliminate them.

     This fundamental level of research cuts across all of the autoimmune diseases. The productive interaction among investigators who study the particular spectrum of the autoimmune diseases, such as the thyroid diseases, multiple sclerosis, lupus, rheumatoid arthritis, the inflammatory bowel diseases, and many more, will teach us the basic lessons necessary to devise more effective, long-term treatments for the broad range of autoimmune diseases.

A major problem needs major response

     Another important reason that we should begin to view the autoimmune diseases as a unified group is to give them greater visibility. Most autoimmune diseases are relatively rare, and most are not fatal. Therefore, they never appear on the public "radar screen" as a serious health problem requiring more attention and more funding. Taken together, however, the autoimmune diseases occupy the third or fourth place in the list of prevalent diseases in our country.

     The majority require lifetime care and treatment, which is an expensive budget item both for the individual and the country. Moreover, an autoimmune disease is debilitating for the patient and often destructive of a productive lifestyle of an entire family.

     It is time, then, that we start to think of the autoimmune diseases as a unified group and to gather our forces on the battleground for a major investigative attack on the fundamental problem.