Two researchers at Saint Louis University's division of rheumatology in the department of internal medicine have been awarded a $1.8 million NIH grant to study the physiological and biochemical functions in lupus, an autoimmune disease, and develop possible new medications for its treatment.
Lupus, a chronic inflammatory disease, occurs when the body's immune system produces antibodies that attack its own tissues and organs, and affects different parts of the body including kidneys, blood cells, brain, heart and lungs. Terry Moore, M.D., director of rheumatology and Anil Chauhan, Ph.D., associate professor in the division of rheumatology at SLU will study and evaluate the role of T-cells and immune complexes in the disease, and how they generate inflammatory responses.
A T-cell is a lymphocyte - a type of white blood cell - that protects the body's immune system against infection and abnormal immunologic processes. Usually, antigens bind to antibodies, forming immune complexes that are part of a normal physiological process to remove undesired proteins from blood circulation. But in lupus patients, as these complexes continue to circulate in the body, they lead to excessive inflammation and produce bad T-cells, which lead to tissue damage and organ failure. Moore said that they have found receptors on T-cells that were not recognized before. Receptors are the surface on the cell that selectively receive and bind specific substances. Moore and Chauhan found that the binding of these complexes with Fc receptors, a kind of receptor, can affect treatment of lupus patients.
"We are just trying to understand the basic immunologic mechanisms of the disease," said Moore. "By understanding those, we can set up better therapy for lupus."
Moore also said that the broader aim of the research is to understand the pathology of the disease and monitor changes in the T-cells and study how well the suggested therapy and drug are working.
"We want to figure out how immune complexes that are present during the disease pathology change the normal T cells into bad T-cells," said Chauhan, co- principle investigator on this project. "If we can block this development of bad T-cells that are present in lupus patients, we will be able to develop a new therapeutic drug."
The grant is based on a unique capture technology for isolation of immune complexes developed by Chauhan. A recent study published in the Journal of Biological Sciences found that the immune complexes could activate CD4+ T cells, also known as helper cells, which lay the foundation for the research being done by Moore and Chauhan.
The five-year project will involve evaluation of T-cells in 100 lupus patients. Chauhan with Richard DiPaolo, Ph.D., assistant professor in the department of molecular microbiology and immunology at SLU, will also conduct an experiment in which they will remove the normal T-cells from a set of mice and implant the bad T-cells from the lupus patients in them. They will then monitor the mice and look for any development of lupus, which will be treated with potential drugs.
"If we develop a new drug, it will really help patients," said Chauhan. "In the last 30 years there has been only one successful new drug for lupus; we need many more alternative therapies."
Moore said lupus is the most common disease in young females of all races in the United States, especially African-Americans.
"With more specific findings, we may be able to address specific medications with fewer side effects," he said.
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