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Dr. Harley:

Dr. Harley 101
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Dr. Harley's CV in brief

Publications

Arthritis and Immunology Research Program

John B. Harley, M.D., Ph.D. Member and Program Chair, Arthritis and Immunology Research   Program James R. McEldowney Chair, Professor of Immunology, University of Oklahoma   Health Sciences Center George Lynn Cross Research Professor, University of Oklahoma Health Sciences   Center Professor of Medicine, Department of Medicine, University of Oklahoma Health    Sciences Center Adjunct Professor, Departments of Microbiology and Pathology, University of   Oklahoma Health Sciences Center Staff Physician, U.S. Department of Veterans Affairs Medical Center, Oklahoma   City

Research Interests
Systemic lupus erythematosus is an autoimmune disease primarily afflicting younger women. When left untreated, it can cause kidney failure, destruction of the blood cells, memory and thinking problems, strokes, heart attacks, arthritis and other serious health problems. For more than two decades we have studied the immune response and genetics of this disease.

Recognizing the strong genetic tendency of lupus, we have collected biological samples and data from more than 475 families having a member with the disease. In addition, we have collected this information from approximately 500 families having two or more afflicted members. We have identified 18 robust genetic linkages, established with LOD>3.2 or p<0.00005 and confirmed with independently ascertained pedigrees. Of these, we have identified three genes linked to lupus: HLA-DR (allele 3), FcyRIIIA (F176V) and PDCD-1 (a transcription activator). The focus of our current work is on identifying the genes responsible for the other 15 robust linkages, exploiting the extraordinary technological advances that have accompanied the Human Genome Project. We will be working to establish these genetic associations and to describe molecular mechanisms of disease that involve these genes.

We are also working to identify environmental factors in lupus. Our data suggest that for anti-Sm initiated lupus, autoimmunity arises through a molecular mimicry mechanism from the heterologous humoral immune response directed against Epstein-Barr virus nuclear antigen-a (EBNA-1). Recently, an analogous mechanism has been des-cribed for anti-Ro. Together, patients with anti-Sm and anti-Ro comprise over one-third of human lupus cases.

We have firmly established an association of Epstein-Barr virus infection with lupus, using multiple methods to test different groups that vary primarily in age. Results compiled from these experiments suggest that lupus begins before Epstein-Barr infection and progresses successively through EBNA-1 heterologous immunity, molecular mimicry with self-antigens, and benign autoimmunity, culminating in pathologic autoimmunity and disease. All of our environmental data are consistent with this model, with some of these results providing powerful statistical evidence that strongly supports its validity. Our future work will concentrate on testing and refining the details of immune function in this model.

Joined OMRF Scientific Staff in 1982.

Mailing Address
Arthritis and Immunology Research Program, MS 24
Oklahoma Medical Research Foundation
825 N.E. 13th Street
Oklahoma City, Oklahoma 73104

Contact Information
Phone: (405) 271-6673
Fax: (405) 271-3980
E-mail: John-Harley@omrf.org