title: How compelling are the data for Epstein-Barr virus being a trigger for systemic lupus and other autoimmune diseases?
abstract: OBJECTIVE
  Systemic lupus erythematosus (SLE) is caused by a combination of genetic and acquired immunodeficiencies and environmental factors including infections. An association with Epstein-Barr virus (EBV) has been established by numerous studies over the past decades. Here, we review recent experimental studies on EBV, and present our integrated theory of SLE development.
  
  
  RESULTS
  SLE patients have dysfunctional control of EBV infection resulting in frequent reactivations and disease progression. These comprise impaired functions of EBV-specific T-cells with an inverse correlation to disease activity and elevated serum levels of antibodies against lytic cycle EBV antigens. The presence of EBV proteins in renal tissue from SLE patients with nephritis suggests direct involvement of EBV in SLE development. As expected for patients with immunodeficiencies, studies reveal that SLE patients show dysfunctional responses to other viruses as well. An association with EBV infection has also been demonstrated for other autoimmune diseases, including Sjögren's syndrome, rheumatoid arthritis, and multiple sclerosis.
  
  
  CONCLUSIONS
  Collectively, the interplay between an impaired immune system and the cumulative effects of EBV and other viruses results in frequent reactivation of EBV and enhanced cell death, causing development of SLE and concomitant autoreactivities.
authors.affiliation: aDepartment of Autoimmunology and Biomarkers, Statens Serum Institut, Copenhagen bDepartment of Systems Biology, Technical University of Denmark, Kongens Lyngby, Denmark.
authors.forename: Anette
authors.initials: A
authors.lastname: Draborg
authors.forename: Jose M G
authors.initials: JM
authors.lastname: Izarzugaza
authors.forename: Gunnar
authors.initials: G
authors.lastname: Houen
mesh_terms: D001172:Arthritis, Rheumatoid / Q000276:immunology / Q000821:virology; D001327:Autoimmune Diseases / Q000276:immunology / Q000821:virology*; D020031:Epstein-Barr Virus Infections / Q000150:complications*; D019317:Evidence-Based Medicine / Q000379:methods; D004854:Herpesvirus 4, Human / Q000302:isolation & purification / Q000502:physiology; D006801:Humans; D008180:Lupus Erythematosus, Systemic / Q000276:immunology / Q000821:virology*; D012859:Sjogren's Syndrome / Q000276:immunology / Q000821:virology; D014775:Virus Activation / Q000276:immunology