Clinical and molecular evidence for association of SLE with parvovirus B19.
In addition to genetic and environmental factors, viruses have been suspected as causes and/or contributors to human autoimmune diseases, although direct evidence for the association is generally lacking. Parvovirus B19, the cause of Fifth disease in childhood, and possible trigger in the spectrum of autoimmune diseases in adults, has emerged as one of the central viral candidates within the last few years. In this article we propose a possible model for parvovirus B19 association with systemic lupus erythematosus (SLE). The basis for our model is the secretion of hydrolyzing anti-ssDNA autoantibodies in 30-70% of cases with SLE, which in turn can either hydrolyze viral B19 ssDNA in blood and other fluids, or intranuclear, replicated viral ssDNA after re-activation and translocation of the virus into the nucleus of the host permissive cells. Both mechanisms contribute to perpetuation and maintenance of a 'vicious cycle' with concomitant flares in SLE, and involve inevitable TLR9 sensitization and genetic switch for anti-ssDNA autoantibody production from activated B cells in individuals prone to triggering. This model strongly suggests a major potential impact upon early prevention (vaccination) and targeted therapy of this subclass within the SLE spectrum of diseases. Incorporated in this new concept is an innovative idea for developing the tool for more precise (individualized) diagnosis, prevention, and therapy.
Department of Computer and Electrical Engineering and Computer Science, Florida Atlantic University, FL, USA. mpavlovi@fau.edu
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Pavlovic
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Kats
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Cavallo
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Shoenfeld
D000328:Adult; D000818:Animals; D001323:Autoantibodies / Q000097:blood; D002648:Child; D004277:DNA, Single-Stranded / Q000276:immunology / Q000378:metabolism; D004279:DNA, Viral / Q000276:immunology / Q000378:metabolism; D006801:Humans; D008180:Lupus Erythematosus, Systemic / Q000821:virology*; D010322:Parvoviridae Infections / Q000150:complications* / Q000276:immunology / Q000821:virology; D016732:Parvovirus B19, Human / Q000276:immunology / Q000302:isolation & purification*; D051217:Toll-Like Receptor 9 / Q000276:immunology; D014765:Viral Vaccines / Q000276:immunology
D001323:Autoantibodies; D004277:DNA, Single-Stranded; D004279:DNA, Viral; D051217:Toll-Like Receptor 9; D014765:Viral Vaccines