So they treated 35 patients. 15 had EBV, of which 12 were responders. 20 did not have EBV, of which 6 were responders.
If it is EBV, why did 6 out of 20 without EBV respond?
EBV is a Herpes-Virus, it is also called HHV-4. Why did they not test for other Herpes-Viruses? Like HHV-8 (which is latent in B-cells as well), HHV-6, CMV (HHV-5) and VZV (HHV-3)? Is the correlation better when considering most (or all) known human herpes viruses?
Furthermore, these are awfully small sample sizes. Does it hold up in larger sample sizes? My experience is, that with EBV (and herpes viruses) researchers get all excited because they find some spurious correlation in small samples sizes and when the correlation evaporates in larger studies, you don't hear much about it (like Montoya's work).
The question of other herpes viruses is quite reasonable. The non-EBV responders may have had different infections in which B-cells were involved.
A different problem is that all EBV is not created equal, even beyond the major strains found in different parts of the globe. If you have any doubts about the ability of EBV to carry insertions in its genome I can supply references. The mechanism by which herpes viruses insert genetic material is about as selective as a shotgun blast.
Much of the work dismissing the importance of EBV in autoimmune disease took place at a time when nobody knew it had three latent states, some of which could replicate DNA without causing lysis. If tests were based on antibodies to proteins present in lytic replication they could miss cases in which DNA replication would only be found by looking for antibodies to early enzymes.
This becomes important when EBV infects B-cells undergoing clonal expansion in response to unrelated antigens. The number of infected cells can increase dramatically without much lysis. Increases in early proteins could get lost in the noise of immune response to an unrelated pathogen. In human terms we might say this is an example of a "false-flag recruitment". I doubt humans were the first to invent this form of deception.
While dismissing studies of autoimmune disease with small sample sizes you might consider
this study about MS and EBV. The incidence of MS in EBV-negative patients is so low you have to seriously consider false negatives. If this sample size is not enough, I doubt it is possible to conduct research on MS and viral infection that would meet your standards.
The connection between EBV and Burkitt's lymphoma is well established, and so are connections with several other cancers. You can argue this in two ways: 1) that the strains of EBV causing cancer contain sequences not found in other EBV; 2) that the increased incidence is the result of a different kind of immune dysfunction, which we don't know much about. Interactions with other pathogens in the environment cause me to favor the latter. If the former alternative is true, then I believe dismissing connections with generic EBV in other diseases is bad research practice, and irresponsible. You could dismiss the connection between HPV and cervical cancer as very uncertain if you accidentally omitted the particular strains responsible, out of more than 100.
Immune system response to EBV is a road to insight into how response to viral infections works in a number of pathological situations. If we really understood this I doubt we would have so much trouble treating viral infections. If depleting B-cells has significant benefits in some subset of patients it should be obvious that we need to find out what a subset of cells are actually doing in those cases where treatment works. Current levels of discourse on the subject are too often simply replays of past disputes.
Many years of work on RA have done nothing to reduce incidence in the general population. How would you advise governments to reduce future costs associated with RA, assuming you don't favor euthanasia? Large sample sizes are necessarily tied to large funding, not innovation. Funding nine ideas with little chance of success to get one good idea would not be more expensive the last few decades of experience. (Ask Google about long shots.) If anyone wants to break out of the current stalemate I'd suggest they change current funding approaches.
) I will definitely update. Thanks for answering.
