Associate Professor Marko Radic of The University of Tennessee Health Science Center Authors Paper on Immune System Disorders

Dr RadicAbout one person in 20 develops an autoimmune disorder. These range from rheumatoid arthritis, lupus, or multiple sclerosis, to other progressive autoimmune syndromes. A number of neurodegenerative and age-related disorders, as well as other chronic inflammatory afflictions, also have an underlying immune contribution.

Marko Radic, PhD, of the University of Tennessee Health Science Center (UTHSC), in collaboration with colleagues at the University of Chicago and the University of Pennsylvania, offered insight into what protects healthy immune systems from developing autoimmune disease in a paper published in the July 16 issue of the Proceedings of the National Academy of Sciences (PNAS). Their findings in the PNAS, one of the world’s most-cited multidisciplinary scientific journals, indicate that the body’s method of fighting off autoimmune disease may trigger proteins that have detrimental effects on the body.

Autoimmunity, once started, is difficult to stop, and usually progresses to a chronic and debilitating condition. Previous work had established that powerful and nearly fail-safe mechanisms prevent autoreactive B cells (lymphocytes) from producing potentially destructive autoantibodies.

Dr. Radic, an associate professor in the Department of Microbiology, Immunology and Biochemistry at UTHSC, designed an experiment that stacked the deck in favor of destructive autoreactive antibodies. His team used mice possessing genetic material that encoded an antibody that is common in Systemic Lupus Erythematosus (SLE) or lupus.

Dr. Radic and his team found that the genetically modified mice exhibited three ways of dealing with the autoreactive antibody. One set of B cells extinguished autoreactivity and produced innocuous antibodies. A second set of cells also greatly reduced autoreactivity of their antibodies, but the third set proved a surprise. This population of cells produced strongly autoreactive antibodies of the sort one would find only in lupus, but the antibodies were fashioned into a stiff, glue-like substance or “amyloid.” These autoantibodies stayed associated with the B cells for an extended time before dissociating in the form of insoluble amyloid deposits. It has been argued that amyloid deposits in tissues can lead to various problems. In Alzheimer’s disease, amyloids in the brain contribute to progressive neurological damage.

“We conclude that, with a finite probability, the healthy immune system will generate the precursors of B cells, whose products can cause not only autoimmune disease, but other disorders that are not typically associated with a failed immune tolerance,” explained Dr. Radic. “After nearly a decade of concentrated work with colleagues who share our interests and goals, we were able to achieve this breakthrough.”