B-cells role in disease?

[renerdrat]

I was reading on one of the news updates about cfs http://phoenixrising.me/archives/26930
and came across b-cells.

There's a drug, rituximab that eliminates b-cells, in the trial something like 65% recovered. I'm wondering if there's other ways of reducing b-cells.

Anyway, am curious of peoples thoughts on this

 

[Bob]

Hi renerdrat, in case you weren't aware, we have a whole subforum dedicated to news and discussions about rituximab where you'll find loads of interesting info and discussions...
http://forums.phoenixrising.me/index.php?forums/rituximab-news-and-research.71/

I think steroids reduce b cells, by a degree, but long-term treatment with steroids can cause unwelcome complications. There are some discussion about steroids in the rituximab section too.

 

[renerdrat]

Hi renerdrat, in case you weren't aware, we have a whole subforum dedicated to news and discussions about rituximab where you'll find loads of interesting info and discussions...
http://forums.phoenixrising.me/index.php?forums/rituximab-news-and-research.71/

I think steroids reduce b cells, by a degree, but long-term treatment with steroids can cause unwelcome complications. There are some discussion about steroids in the rituximab section too.

oops I didn't see that, thanks

 

[anciendaze]

The problem is not that B-cells are bad, it is that some subset of B-cells is behaving badly, and we don't know what distinguishes them from healthy B-cells. (This situation has gone on way too long. It is possible to separate precisely the CD20+ B-cells that Rituximab depletes, without killing them, using flow cytometry. You can then run experiments in vitro to see how they respond to different kinds of stimulation, and compare this with the response of cells from healthy people. You don't have to experiment on complete humans.) There is other evidence that NK cells are either reduced in number or less effective. There is even evidence of cytotoxic T-cells invading tissues where they contribute to damage. This leads me to suspect there are problems in signalling between different components of the immune system. One research paper on this subject appeared this year, but did not specifically address ME/CFS. This doesn't bother me much, because I'm convinced the disease has been defined in a way that makes useful research nearly impossible.

There have been reports of clusters of rare leukemia/lymphomas in patients since the 1980s, including B-cell lymphomas, with some reason to believe incidence is many times higher in this population. From a clinical standpoint the only distinction that seems to apply is that a B-cell lymphoma is a "real disease" that kills people, while CFS is not. During the prodromal phase of many leukemias/lymphomas it is simply impossible to distinguish from ME/CFS. The only way to be sure is to wait until the patient develops the "real disease". This diagnostic standard resembles reasoning that the light in the refrigerator must be off when the door is closed.

 

[ScottTriGuy]

...

There have been reports of clusters of rare leukemia/lymphomas in patients since the 1980s, including B-cell lymphomas, with some reason to believe incidence is many times higher in this population. From a clinical standpoint the only distinction that seems to apply is that a B-cell lymphoma is a "real disease" that kills people, while CFS is not. During the prodromal phase of many leukemias/lymphomas it is simply impossible to distinguish from ME/CFS. The only way to be sure is to wait until the patient develops the "real disease". This diagnostic standard resembles reasoning that the light in the refrigerator must be off when the door is closed.

Curious - do folks in this prodromal phase of leukemia / lymphoma experience post exertional malaise?

 

[anciendaze]

Curious - do folks in this prodromal phase of leukemia / lymphoma experience post exertional malaise?

Most such evidence is anecdotal, like the report from Dr. Michael Snyderman, an oncologist/hematologist who was diagnosed with "CFS" a year before he showed clinical evidence of chronic lymphocytic leukemia. This is by no means an isolated example; it is noteworthy because the patient is also a specialist in treating the disease.

(His case became involved in the controversy over XMRV. He has been experimenting on himself with antiretroviral drugs, and his tests do show the "numbers" changing in response to changes in medication, though this does not tell us which retroviruses, including HERVS, might be responsible. He remains alive, longer than expected without conventional treatment for CLL. The fact that he needs to periodically change medication to control disease is no different from patients with known HIV infection.)

If we had more research on PEM we might be able to say. Severe fatigue, which gets worse after exercise, is typical, but current research on PEM has only found the characteristic prolonged drop in VO2 max and anaerobic threshold in ME/CFS patients. Nobody has even been looking for this in other patients, and while some MS patients report something similar I don't see how research requiring MS patients to exercise to exhaustion could pass ethics review. This is a classic Catch-22 situation: if you have either MS or leukemia/lymphoma you can't be tested for the known distinctive characteristics of PEM. If we had better research criteria we might be able to detect the biochemical changes without risking patient relapse. You can find lots of work based on psychological hypotheses and measurement by questionnaires. You can even find some such in MS and leukemia/lymphoma. What these results mean is questionable.

Added: the possibility that a single cause could result in such different diseases should not be too surprising. HTLV-1 is known to cause both a neurodegenerative disease (HAM/TSP) and adult T-cell leukemia (ATL). We have also learned that the majority of those infected are asymptomatic for up to 40 years. Properly functioning immune systems can cope with the infection.