NK cells hold the key to interferon-free therapies
Rheumatology – January 2016 - View Full PDF
Donald D. Anthony Jr., MD, PhD
Rheumatologist, Division of Rheumatology, University Hospitals Case Medical Center and Louis Stokes Cleveland VA Medical Center; Associate Professor of Medicine, Case Western Reserve University School of Medicine
Natural Killer (NK) cells were identified in the early 1980s as being capable of killing tumors or virally infected cells without any prior exposure to the virus, differing from T or B cells in that they require no memory. Though they have long been attractive as cancer-fighting cells, harnessing their power has been elusive.
A project funded by the Veterans Affairs central office and the NIH, to Case Western Reserve University School of Medicine, led by University Hospitals rheumatologist Donald D. Anthony Jr., MD, PhD, is evaluating the role of NK cells in host defense mechanisms in hepatitis C infection to better understand how the interferon response mechanism may work during chronic viral infection.
One of the projects is looking at the role of systemic immune activation and aging on host response to new antigens, or new pathogens, by observing how the immune system state before immunization with a vaccine predicts whether somebody will respond to the vaccine. A number of cells and cytokines are known to be involved in this, but a recent endeavor is to fully understand how prior activation of the system can make the host less able to respond. This applies to the settings of chronic viral infection as well as to autoimmune disease, where the immune system is activated either by dealing with pathogens or because of autoimmunity.
It is also known that in hepatitis C infection, specific genotypes of NK cells are associated with the ability of the human host to resolve infection on its own. Dr. Anthony believes that NK cells and interferon work together to help clear hepatitis C infection during interferon-based therapy. However, interferon therapy has many unwanted side effects. Dr. Anthony hopes that understanding how NK cells help fight viral infection will lead to the development of new treatment strategies for hepatitis C and other viral infections.
Highly morbid outcomes of some hepatitis C infections include formation of autoantibodies and vasculitis, which can lead to kidney failure, nerve problems and even death. Additional contributors to such outcomes include cold precipitable immune complexes composed of rheumatoid factors. Another goal of Dr. Anthony’s lab is to understand how these autoantibodies are produced during hepatitis C infection, so that better treatment strategies can be developed.
For more information or to contact Dr. Anthony directly, please call 1-216-368-3540.
All National Institutes of Health (NIH) funding for basic and clinical research is awarded to the School of Medicine at Case Western Reserve University.