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Lupus, Vol. 15, No. 11, 768-777 (2006)
DOI: 10.1177/0961203306070009

The curiously suspicious: a role for Epstein-Barr virus in lupus

J B Harley

Oklahoma Medical Research Foundation; Deparments of Medicine and Pathology, Oklahoma University Health Sciences Center; Veteran's Affairs Medical Center, Oklahoma City, Oklahoma, USA

I T W Harley

J M Guthridge

Oklahoma Medical Research Foundation

J A James

Oklahoma Medical Research Foundation, 825 NE 13th Street, Oklahoma City, OK 73104, USA. jamesj{at}omrf.ouhsc.edu; Deparments of Medicine and Pathology, Oklahoma University Health Sciences Center

While the events initiating the development of autoantibodies in systemic lupus erythematosus (SLE) have not yet been convincingly established, newly developed tools for molecular investigation make such an undertaking increasingly practical. Applied to the earliest events in the sequence culminating in lupus autoimmunity, we present a critical potential role for Epstein-Barr virus (EBV) in the development and perhaps perpetuation of SLE. The expected properties for an environmental risk factor for SLE are found in this virus and the human host response against it. Existing data show the molecular progression to autoimmunity observed in SLE patient sera, the discovery of the first autoimmune epitopes in the Sm and Ro autoantigen systems, and the possible emergence of these autoantibodies from the heterologous antibodies against Epstein-Barr nuclear antigen-1 (EBNA-1). Further, existing data demonstrate association of SLE with EBV infection, even preceding the development of autoimmunity. Finally, the data are consistent with a proposed model of lupus pathogenesis that begins with antibodies to EBNA-1, predisposing to immune responses that develop crossreactive autoantibodies that culminate in the development of SLE autoimmunity.

Key Words: cross-reactive antibodies • Epstein-Barr virus • environmental risk factors • etiology • molecular mimicry • review • systemic lupus erythematosus


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