MedicalResearch.com Interview with:
John B. Harley, MD, PhD
Professor and Director
David Glass Endowed Chair
Center for Autoimmune Genomics and Etiology (CAGE)
Department of Pediatrics
University of Cincinnati
Cincinnati Children’s Hospital Medical Center
Cincinnati, Ohio 45229
MedicalResearch.com: What is the background for this study?
Response: Previous work has shown that Epstein-Barr virus infection is associated with systemic lupus erythematosus and studies of the origins of the autoimmune response have also suggested that the autoimmunity of this disease may originate with the immune response against this virus. In the meantime, many investigators have been studying the genetics of lupus over the past 25 years. They have found about 100 convincing genes that alter the risk of developing lupus.
MedicalResearch.com: What are the main findings?
Response: If the virus and the genes are even partly responsible for causing lupus, then they should be working together. We tested a prediction for proteins called “transcription factors” that bind DNA to help decide which genes are expressed and which are not. If Epstein-Barr virus is involved then we would expect that the transcription factors would be concentrated in or near the genes that change the risk for lupus. This is dramatically true for EBNA2 (Epstein-Barr virus nuclear antigen 2), a transcription co-factor that is made from the viral DNA and not from the DNA of the infected person.
It turns out that this observation is not only true for lupus, but is also observed for multiple sclerosis, rheumatoid arthritis, inflammatory bowel disease, type 1 diabetes, juvenile idiopathic arthritis, and celiac disease. These results suggest that Epstein-Barr virus may be involved in the origins of at least some of the patients with these diseases.
The finding that transcription factor binding is concentrated across the genes that change risk is found in our report in 2,264 examples in 94 diseases and physiological phenotypes (e.g., height) that suggest a way to understand how genetic differences alter our experience of life.
MedicalResearch.com: What should readers take away from your report?
Response: Readers should understand the understanding mechanisms of disease empowers scientists to interfere in ways that result in better outcomes for patients by developing effective strategies for new therapeutics, management and preventive measures.
Your readers should appreciate that the circumstantial evidence has become much more convincing that Epstein-Barr virus is involved in causing at least some of the patients with lupus, as well as the other diseases whose genetics shows these unanticipated associations with the human DNA that is indirectly bound by EBNA2.
MedicalResearch.com: What recommendations do you have for future research as a result of this work?
Response: The challenge in this area of medical research is to understand the detail of gene regulation so that this knowledge can be used to change the outcome of diseases.
J Harley, et al. Transcription factors operate across disease loci, with EBNA2 implicated in immunity. Nature Genetics DOI: 10.1038/s41588-018-0102-3 (2018).
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