Epstein-Barr Virus in Systemic Lupus Erythematosus, Rheumatoid Arthritis and Multiple Sclerosis—Association and Causation
Abstract
:1. Introduction
2. Evidence of Association
2.1 Serological Data
2.2 Infectious Mononucleosis
2.3 Cellular Immunity
2.4 EBV Viral Load and Expression of Viral Genes in Blood
2.5 Detection of Virus in Diseased Organs
SLE | RA | MS | References | |
---|---|---|---|---|
Increased EBV seroprevalence | + | – | + | [11,12,13,14,15,16,17,18,19,20], [36], [39] |
Elevated serum titers of anti-EBV antibodies | + | + | + | [14], [15], [21,22,23,24,25,26,27], [35,36,37] |
Elevation of antibodies predates symptoms | + | – | + | [24,25,26,27], [38] |
Association with infectious mononucleosis | – | – | + | [52,53,54,55,56] |
Aberrant systemic T-cell response against EBV | + | + | + | [37], [48], [57,58,59,60,61,62,63,64,65,66,67,68,69,70] |
Increased local T-cell response against EBV | N/A | + | + | [49], [71,72,73,74] |
Increased EBV viral load in blood | + | + | +/– | [28], [31], [37], [58], [60], [70], [78,79,80,81,82,83], [85,86,87] |
Virus detected in diseased organ | N/A | +/– | +/– | [81], [88,89,90,91,92,93,94,95,96,97,98,99,100,101,102,103,104,105], [107] |
3. Viral mechanisms
3.1 Infection and Immortalization of Autoreactive B-cells
3.2 EBV Infection of Other Cell Populations
3.3 Innate Immunity
3.4 The State of EBV Infected B-cells in a Chronically Inflamed Environment
3.5 Transactivation of Human Endogenous Retroviruses
4. Immunological Mechanisms
4.1 Molecular Mimicry and Mistaken Self
4.2 Bystander Activation and Epitope Spreading
4.3 Dual and Chimeric TCRs
4.4 Polyspecific B-cell Activation
4.5 Accumulation of EBV-specific CD8+ T-cells in Sites of Inflammation
5. Conclusions
Conflict of Interest
References
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Lossius, A.; Johansen, J.N.; Torkildsen, Ø.; Vartdal, F.; Holmøy, T. Epstein-Barr Virus in Systemic Lupus Erythematosus, Rheumatoid Arthritis and Multiple Sclerosis—Association and Causation. Viruses 2012, 4, 3701-3730. https://doi.org/10.3390/v4123701
Lossius A, Johansen JN, Torkildsen Ø, Vartdal F, Holmøy T. Epstein-Barr Virus in Systemic Lupus Erythematosus, Rheumatoid Arthritis and Multiple Sclerosis—Association and Causation. Viruses. 2012; 4(12):3701-3730. https://doi.org/10.3390/v4123701
Chicago/Turabian StyleLossius, Andreas, Jorunn N. Johansen, Øivind Torkildsen, Frode Vartdal, and Trygve Holmøy. 2012. "Epstein-Barr Virus in Systemic Lupus Erythematosus, Rheumatoid Arthritis and Multiple Sclerosis—Association and Causation" Viruses 4, no. 12: 3701-3730. https://doi.org/10.3390/v4123701