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SCIENTIFIC PUBLICATIONS BY ALR FUNDED RESEARCHERS

The CR2:C3d receptor: ligand interaction as a therapeutic target in lupus

Holers, Michael, MD

University of Colorado Denver, AMC and DC

Two components of the immune system are CR2 and C3d. CR2 is a receptor of a type of white blood cell, lymphocytes. C3d is capable of binding to germs and other things the human body may attack. In a healthy person, CR2 and C3d are part of the apparatus through which the body creates antibodies. After C3d binds to germs, it attaches to CR2. Excessive activity of CR2 and C3d lead to the creation of antibodies harmful to people with lupus.

Recently, the Holers’ lab has been able to develop a strategy and the tools that will allow the testing of novel inhibitors of both CR2 and C3d. These tools are monoclonal antibodies, one of which zeros in on CR2 and blocks its functioning, without directly affecting other closely related receptor interactions. The second tool is a monoclonal antibody that zeros in on the C3d fragment and blocks the interaction of C3d with CR2 and does so without affecting any other function of C3. C3d is a tiny fragment of C3.

Once these tools are in place, the researchers will use a mouse model of lupus to test the scientific hypothesis that disruption of the attachment of C3d and CR2 will reduce the way the mouse’s germ fighting system attacks the mouse’s own tissues, causing disease. 

What this study means for people with lupus: Dr. Holers hopes the current research will lead to new, effective therapies that target the CR2-C3d interaction. It is hoped that the approach will permit limiting or eliminating the amplifying effect of the CR2-C3d interaction. 


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