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Shedding Light on Autoimmune Links
Study of BAFF-R protein could yield new treatment strategies

Wasif N. Khan, Ph.D., center, working with Jacqueline Wright, left, and Iris Castro, Ph.D., right, has identified a protein that likely affects cytokine function in autoimmune patients.

It’s common knowledge in the research community that B and T lymphocytes contribute to autoimmune diseases. “But we don’t know how,” says Wasif N. Khan, Ph.D., a professor of microbiology and immunology who has been doing research in the field for seven years.

It is also known that autoimmune diseases are caused by cells turning against struc-tures within our bodies. “Normally the immune system gets rid of such cells from the body through tightly controlled mechanisms,” adds Khan. “We wanted to know what makes some clones of B cells, which are self-destructive, escape these mechanisms, become aggressive in their growth and sur-vival properties, and continue destruction.”

While some researchers have looked at how B cells use specific receptors to destroy specific tissue, others have investigated cytokine BAFF, a circulating protein that increases the metabolic fitness of B cells and is produced more heavily in autoimmune patients. Khan, working with Iris Castro, Ph.D., a post-doctoral associate in the Department of Microbiology and Immunology, and doctoral candidate Jacqueline Wright, took some additional steps. The team was able to uncover the molecules that regulate expression of the receptor for cytokine BAFF, known as BAFF-R, and that can thus cause certain B cells to be more sensitive to the action of BAFF.

The study, published in the Journal of Immunology, noted that the higher expression of BAFF-R supports survival of B cell clones that can damage tissues in autoimmune patients. The team connected the parallel processes of an increased BAFF production with the control of BAFF-R expression, likely a critical link that facilitates escape and survival of self-destructive B cell clones. Certain B cell clones that were supposed to die, says Khan, survive better because they enhance and support the function of the BAFF cytokine through provision of more BAFF-R.

Because there is no cure for autoimmune conditions, Khan believes the goal is to find molecular structures that can be targeted in B cells that cause disease. What could result are new therapies that, unlike immunosuppressant drugs, will serve the patient’s needs without suppressing the function of the entire immune system.