Scleroderma, rheumatoid arthritis, systemic lupus, and multiple sclerosis are diseases where the immune system is not working normally. Instead of reacting only to what is foreign and potentially dangerous, such as invading infectious organisms, the immune system also reacts against some of its own normal tissue. This is called "autoimmunity", in other words, immunity against self. The purpose of our work in autoimmune disease is to figure out why this occurs. Currently there is no treatment involved.
These are the diseases we currently study:
The term scleroderma means hardening of the skin. Scleroderma is characterized by the formation of fibrous tissue (fibrosis). Systemic sclerosis involves more widespread fibrosis including the digestive system, lungs, kidney and heart. There is also inflammation of vessels (vasculopathy).
Systemic sclerosis comes in two forms, diffuse and limited which are defined by the extent of skin involvement, although more extensive internal organ involvement accompanies more extensive skin involvement (diffuse disease). Limited disease is usually less severe, involving the skin and, to a lesser extent, internal organs such as the digestive system.
Scleroderma affects women more frequently than men. Scleroderma begins to be more frequent in women in their 20's and 30's, increasing further in the 40's and 50's. Because these are years following the time of childbearing, we have asked whether changes to the immune system that happen during pregnancy predisposes a woman to the later development of scleroderma.
Rheumatoid arthritis is an autoimmune disease that affects more than 2.5 million people in the United States and is diagnosed by typical symptoms and characteristic patterns of joint disease. Rheumatoid arthritis is an inflammatory autoimmune process affecting the joints and sometimes other tissues. Current therapy is directed toward diminishing the inflammatory response and treating the uncontrolled inflammation.
Rheumatoid arthritis gets better or even goes away entirely for most women during pregnancy. This is not explained by changes in sex hormones because taking estrogen and progesterone doesn't make rheumatoid arthritis better. What is unique to pregnancy is that a woman is exposed to an individual who is half-foreign because half of the child's genes are inherited from the father. One of the big mysteries in immunology is why this "half-foreign graft" isn't rejected. We believe that sub-cellular particles from the fetus and placenta leads to tolerance of the fetus and correction of the immune system dysfunction of the mother.
We previously found that remission of rheumatoid arthritis occurred most often when the child had inherited a particular set of genes from the father that were different from the mother's genes. The genes that are important are called HLA class II genes. They are genes that are particularly important in immune responses and to the distinction of self versus foreign.
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Multiple sclerosis is an autoimmune disease that affects the central nervous system (brain, spinal cord, nerves to the eye). The immune system attacks a substance that surrounds the nerves (myelin) as well as the nerve fibers. The result is scarring, disrupting nerve impulses that travel to and from the brain and spinal cord. The course of multiple sclerosis is variable ranging from mild and intermittent to sustained and severe.
Similar to rheumatoid arthritis (but differing from other autoimmune diseases) multiple sclerosis usually improves during pregnancy but returns after delivery. We are currently applying for funding to investigate the reason(s) for pregnancy-induced improvement of multiple sclerosis.