Jaap,
Have you considered the potential for autoimmune reactions related to EBV to be "inadvertent" immune reactions to human proteins contained within a viral envelope?
An observed supporting detail for this is the finding of Vidick and Gillet in 2013 that "several host proteins were found in purified MuHV-4 virions including Annexin A2".
Further, a new abstract from IHW2018 by Li-Chiu Wang, states that "We further found that Anx-A1 was expressed on the envelope of HSV-1 virions."
A humoral immune reaction that is simultaneously directed towards multiple EBV or HSV envelope proteins and to annexin could explain the anti-annexin antibodies seen in Behcet's disease, which has already been strongly linked to the presence of HSV. A similar relationship might exist for EBV and lupus.
Thus, a reaction against herpesvirus envelope glycoproteins such as gB, gC and gE could be slightly mis-targeted, resulting in an antibody response to neighboring proteins such as annexin in the EBV or HSV envelope. The probability of such a reaction seems raised by the fact that annexin also is observed to bind to gE from HSV-1, so some epitopes of annexin could serve as antigens when antibodies are generated that target gE when it is bound to annexin.
There are other examples of autoantibodies seen in chronic neurodegenerative conditions, such as anti-ATP synthase in Alzheimer's and anti-aquaporin in MS. Coincidentally, ATP synthase is observed within the envelope of HSV-1, illustrating a potential pattern of pathogenesis for the autoimmune phenomenon.
An age old practice in vaccine development is the insertion of an immunogen into a neutralized virus such as vaccinia, so there is good precedent for this type of directed antibody generation that's broadly published.
Do you think this hypothesis is worth investigating and testing?
There's some supporting references below for easy checking.
Regards,
Eli Kammerman
Proteomic characterization of murid herpesvirus 4 extracellular virions. PLoS One. 2013 Dec 30;8(12):e83842.
Annexin A1 Binds to Glycoprotein E to Enhance Herpes Simplex Virus I Infection Contact: Li-Chiu Wang, [email protected] http://www.herpesvirusworkshop.com/2018/download?file=abstract
Epstein and Holt paper from 1963 J. of Cell Biology which discusses the finding of ATP synthase in HSV envelope, PDF linked here:http://www.ncbi.nlm.nih.gov/pmc/articles/PMC2106869/pdf/337.pdf
Autoantibodies to the adenosine triphosphate synthase play a pathogenetic role in Alzheimer's disease. Neurobiol Aging. 2012 Apr;33(4):753-66.
Anti-ATP synthase autoantibodies from patients with Alzheimer's disease reduce extracellular HDL level. J Alzheimers Dis. 2011;26(3):441-5.
Add Alzheimer's disease to the list of autoimmune diseases. Med Hypotheses. 2005;64(3):458-63.
Aquaporin 4 antibody positive central nervous system autoimmunity and multiple sclerosis are characterized by a distinct profile of antibodies to herpes viruses.Neurochem Int. 2010 Nov;57(6):662-7.
One more relevant reference to support the argument of autoimmunity being instigated by human proteins such as annexin within the viral envelope:
Isolation and preliminary characterization of herpes simplex virus 1 primary enveloped virions from the perinuclear space.
J Virol. 2009 May;83(10):4757-65.
"We identified most capsid proteins, a tegument protein (VP22), a glycoprotein (gD), and a cellular protein (annexin A2) in the primary enveloped virion preparation. "