Rituximab & "rebooting" the immune system: 2009

I've been reading Jorgen Jelstad's very interesting blog post on Rituximab from last October which includes some very interesting comments from Dr Nancy Klimas among other things, and a link to this 2009 article on how "rebooting" the immune system has helped in MS and rheumatoid arthritis, and might help in ME/CFS (this is the work that led to the Fluge & Mella study. It's also interesting how what was initially a very unpopular hypothesis by a couple of cold-shouldered researchers became mainstream.

As a last resort some patients with severe autoimmune illnesses can subject themselves to bone marrow transplant following complete immuno suppression via chemo. They acquire a new immune system and this causes a complete 'reboot; of the immune system. As in the killing of that that existed and the replacement via bone marrow someone elses...

Interesting comment. many autoimmune illnesses that were thought to be purely innate and cytokine mediated seems to also respond to ritixumab. So explain that

I know of a case of twins with autism who underwent bone marrow transplant for leukemia, and as a consequence lost their autism... I was mentioning this story recently to a couple of scientists (neuroimmunologists), both simultaneously said 'plasmapheresis!' as something that should be tried/researched as a safer alternative. I don't know much about it, except that it is often used as a first-step relief option for autoimmune disease, to be followed later by rituximab etc.

Interesting - here's plasmapheresis on Wikipedia.

Great observation natasa! I believe the Norwegians are testing this idea in 5 patients 2-3 prior to start of rituximab treatment. In the best case scenario it will get more people to repond to rituximab - and quicker!

BMTs are highly dangerous and far from an ideal solution. They chemo can kill you as can infections. Also there are risks from graft vs host disease (where the new imune system attacks the body). I believe that for a full intensity transplant you need to be physically quite well to survive although they can do a less intense version which has a reduced chance of sucess. The imune system is never really the same and you end up on antibiotics for life. Also I believe you are then suseptable to all the normal childhood diseases.

Would chemo such as FLAG-ida restart the immune system? It kills of the bone marrow and allows it to regrow. Its used where there are leaukemia cells in the bone marrow to kill off everything with the hope only good cells will regrow. I think its the first stage of a bone marrow transplant (at lease for leukemia) prior to conditioning chemo and the transplant.

Having said that I know someone who had fibromyalga and the pain went after a bone marrow transplant (for leukemia). Still too soon to really judge though. I think it would be interesting to collect a database of treatments and responses though, I saw that Mella & Fluge started treating people with rituximab after observing its effectiveness when treating people with ME for cancer. Are there other such stories/observations that could give clues or hints?

its already used in POTS where small fiber neuropathy is suspected. Doesnt always work in autoimmune disease and IVIG or immuno suppressants may be required. But its wortha shot in CFS without a doubt and the obviousness of an autoimmune etiology boggles my mind given the female to male ratio of CFS, the often acute onset and the waxing and waning presentation (all common factors in other autoimmune diseases).

I know there is talk of auto-immune issues being cfs, but are people taking it this way as ritux is commonly used for autoimmune conditions, im sort of thinking its being used for a different purpose ie killing b-cells that are potentially infected with viruses, lowering these viruses/viral load then gives the general immune system a boost to kill what other infections are around, then when healthy b-cells are made again we get another boost of infection fighting. Thats how i sort of interperate. Nk dysfunction found i think maybe from just a burnout of too much work and unable to keep up the demand on them, maybe produce immature nk cells and cd8 t-cells.

I get the feeling this is maybe Dr K's idea as he is into the ritux treatments with antivirals??

cheers!!!

What is already used in POTS? Please clarify and expand your comments for those of us with less of a scientific background. I want to understand your thinking better, especially as I agree with the track you are on..

In some ways, the story of Dr. Edwards and the resistance of the medical establishment to RA being a B-cell related autoimmune disorder raises another timely issue: Is being accepted by your professional peers always desirable? If your peers are all going down the wrong road in one big comfortable group, then obviously the answer is - NO. I would suggest that this is a question that ought to be given serious consideration as it applies to the new IACFS/ME journal, Fatigue: Biomedicine, Health and Behavior.

I have a great deal of respect and appreciation for most of the people involved in the IACFS/ME but doctors defer to doctors and disregard patient concerns as coming from the uninitiated who just don't understand all of the factors that must be taken into consideration (professional advancement, funding, and the very real unspoken taboo against even the appearance of criticizing other doctors) far too often and on occasion, at great expense to the patients they are supposed to be helping.

In the case of MS didn't one in seven patients die from this, though the others all recovered?

I believe there are two issues. Firstly death either from the conditioning chemo or from infections.The initial chemo kills the bone marrow, hence the immune system and you are unable to fight infections, even the most trivial infection that most people wouldn't notice will be serious. Some can be fought with antibiotics, anti-virals and anti fungals but others cann't or can get too bad. I believe they are developing granucite donations to help fight really bad infections which could make the process safer.

Infection is one of the reasons it is so expensive. In the UK at least they keep you in an iscolation ward until white blood counts start to rise and then they like you to be within 40 mins of their ward incase of infections for at least 100 days. So the hospital will have flats near by. After the transplant immune suppressents are used to stop the new immune system attacking the body - but there is then a significant risk of infections that can prove fatal.

My suspicion is that the mortality rates will vary with the level of care. Which is probably dependent on the available budget.

The other big risk is around graft vs host disease (where the new bone marrow fights the body) which can occationally become cronic and highly disabling.

However, they can be quite vicious to another if they step outside the "norm". My Lyme doc was literally run out of state in less than 5 days after upsetting an Infectious Disease doctor. The ID doctor who apparently had high level connections threatened to have not only her admitting privileges but the entire practices' admitting privileges suspended at the local hospital. And my doc's license to practice was put under immediate review. Medicine is an extremely conservative "industry".

Post bone marow transplant they use Rituximab to treat EVB which can otherwise cause lymphomas but the effects are quick in terms of removal of the virus. This would seem to differ from the delays with RA and with Fluge and Mella's study.

http://www.nature.com/bmt/journal/v31/n11/full/1704061a.html

I'm not sure that it helps the immune system recover since it removes b-cells and hence makes you more subseptable to disease.

Your body will replace them with new, healthy b-cells.

Eventually but there will be a natural birth and death rate for b cells. If you suddenly kill all b cells they will not immediately be replaced.

Also depends on if the viruses are irradicated from other tissues of the body or b-cells will get reinfected again. I think this might be why dr K is looking into antivirals with ritux, i think this might be a way of reducing the amount of ritux treatments needed. This might also be why dr lerner has patients on antivirals for a number of years as he waits for the viruses and cells infected with the viruses to die off. i think the combo of treatments will be the answer. But one last thing though, will the immune system/nk function return to normal with this or there is the potential for this whole cycle to happen again if one comes in contact with someone with an active infection??

cheers!!!