Related Diseases Association
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Noel R. Rose, M.D., Ph.D.
The topic that Mrs. Ladd has asked me to discuss with you this afternoon is "Autoimmune Diseases: How Are They Related?" It is a very good topic because it forced me to think about the question.
First, what do we mean by autoimmunity or autoimmune disease? We're all familiar with the term immunity now that AIDS has become so prominent. To encapsulate the word, it means, essentially, resistance to disease. Usually we are speaking of infectious disease, and immunity comes through experience with the disease. If we've had mumps as children, we know that we are not susceptible to a second episode of mumps. We say that we are immune to mumps. If we have chicken pox as children, we know that we are immune to chicken pox, generally, for the rest of our lives. If we have measles as children, we know that we do not get measles a second time. If we are vaccinated or immunized, we acquire our immunity through an artificial means. Children will be vaccinated against polio; they will be vaccinated against diphtheria and tetanus. Therefore, we can acquire immunity, either through natural exposure to the disease or through artificial means, such as vaccination. Originally, then, immunity, was thought of as the body's way of defending itself against disease.
One of the basic precepts of immunity, going back to the very early days of the 20th century, has been that if immunity is going to benefit us, it has to be directed to something foreign, something outside of the body. So it has always been a precept of immunologists that the immune response only concerns foreign material. When I began in this field--40 years ago--almost everyone believed that immunity could be directed exclusively against foreign materials. That idea implies that there is some mechanism by which the body can distinguish what is itself from what is not itself--we now say the immune response shows self, non-self discrimination.
What happened about 40 years ago? Well, a number of key
discoveries were made--some of them in my own laboratory--which
turned that doctrine of self, non-self distinction on its head. We
found that there are a number of instances in which the immune
response is directed to something in the body of the host itself.
It seemed implausible, even contradictory; but, in fact, that was
exactly what we found: there are some circumstances where the
immune response attacks the body of the host itself. The host
may be an animal or it may be a human patient. That is what we
call autoimmunity. Autoimmunity is nothing more than the immune
response directed to the body of the patient himself or herself.
Let me define a second term for you, autoimmune disease. These two terms do not mean exactly the same thing, and the difference may be important to us as we talk about some of these issues a little later this afternoon. Autoimmune disease is a disorder that occurs because of autoimmunity--a disease that is caused by an immune response to the body of the patient himself or herself.
Now, in defining autoimmune disease that way, I imply that there is autoimmunity without autoimmune disease. In fact, we now know that autoimmunity is not at all uncommon and that it exists in all of us. Every one of us has some degree of autoimmunity naturally, and it does not seem to do us any harm. It is, in fact, only a minority of cases where autoimmunity actually produces damage in the body, producing disease. So there are really two basic questions that I, as an investigator, and my colleagues in this field need to unravel.
First question is: How does autoimmunity arise? What causes the body to produce an immune response to itself? What are the circumstances, what are the mechanisms, what are the triggers for the phenomenon that we call autoimmunity? That's one question. That's a very basic question that involves biology, chemistry, even biophysics. It requires a deep understanding of the immune system. We need to know a lot more about how the body produces immunity reactions. We know a great deal, but there are still enormous voids in our understanding. We must know that in order to understand how the body normally distinguishes self from non-self.
The second question is: What are the factors in the autoimmune response that sometimes cause disease? These are the two critical questions that are the topics of basic research. Sometimes the feeling is expressed that basic research is scientists fooling around in the laboratory doing things that are unimportant. Well, there is nothing that is unimportant about these questions. They are absolutely critical. We must understand that if we are ever going to develop effective treatments or, more important, cures for preventing autoimmune disease, we must understand them. Just as we would never have been able to control infectious diseases until we found the bacteria or viruses that cause diseases, so we cannot deal effectively with autoimmune disease until we understand its cause.
Now, let's get to the question Mrs. Ladd put to us: Why are autoimmune diseases related? And here I have to give you a little bit of insider information about how medicine is organized in this country.