I am going to reply to you guys but have to put the disclaimer first that my questions might appear idiotic. I really want to understand this topic (removing autoantibodies) since it most directly relates to my own situation. I will never be one of the great scientific minds of PR... and thank you all for bearing with my questions
I am inquiring why plasmapheresis was not done alone since it is less expensive and more widely available, and no trials to date have this modality for CFS (that I know of). It would have also made for an excellent control group.
Isn't the main difference between PP and IA that in PP the plasma is removed and replaced with blood transfusion or albumin vs. in IA only the autoantibodies are removed and then the plasma is filtered and put back into the body? If this is the main difference, why would it matter which one was done in the study or that PP was less expensive or widely available? (which also varies depending where you are: Europe/Asia vs. the US, etc).
Also, why would one technique (PP vs. IA) change the outcome of the study and what do you mean that "it would have made an excellent control group"? Isn't the control group the one that does not receive the treatment (in this case, the PP or IA) and only receives saline or dextrose (something without the actual med or treatment in it)?
Crossover just means a placebo group and the active group switch during the trial; it is good when a trial has a small amount of participants or it is unethical to withhold treatment.
How would they switch in the middle? Do you mean switch PP to IA, or vice versa, or do you mean switch to plain saline? If the autoantibodies were already removed, how would giving saline change anything? I don't get it!
The researchers pulled out a single antibody. This only matters because a researcher has a financial interest in that antibody.
How would PP or IA only pull out a single autoantibody? Doesn't it (temporarily) remove all autoantibodies from the blood? I have eleven known autoantibodies (and my doctors suspect I probably have more) but wouldn't a treatment like PP or IA pull out even the ones that I did not know that I had?
I also still do not understand what this has to do with financial interest? If you are studying a specific autoantibody(ies), wouldn't you WANT a treatment that targets those autoantibodies?
The scale they use for an outcome is for cancer fatigue, but it is not frequently used even within oncology. It is definitely not used in CFS. It is a good and thorough questionnaire, however there is a lack of data to compare the results. If there was any placebo effect, at all, the results are invalid.
I thought every study has some number of participants in which their improvement is attributed to the placebo effect? Or are you saying that b/c this scale was designed for cancer (not for ME/CFS) it makes it invalid as a measurement and all results become placebo effect?
Also, wouldn't it be possible that some of the participants had symptoms from the autoantibodies that were disabling but were NOT actually ME/CFS? In this case, couldn't it be useful to study these autoantibodies in and of themselves and how they effect people who have them?
I probably made it more confusing not less, but I did the best I could.
No, it is definitely not you and it is me who does not understand! I test positive for 7 of the 9 Cell Trend autoantibodies (plus four other autoantibodies) and really want to understand this but it's possible I never will!
EDIT: Thinking about this more and reading
@alex3619's post below, I now believe I am (and my statement above is) wrong and you are correct. I had never heard of immunoabsorption and was marvled by it because I thought it was absorbed all antibodies, which would be incredible. But it would also be redundant as regular plasmapharesis would achieve the same thing.
So immunoadsorption (IA) only targets a single autoantibody at a time? I thought the difference between PP and IA was what I described above (replacing the plasma vs. returning it to the body after it is filtered). Don't both treatments remove all pathogenic autoantibodies? I know it means that there are two redundant techniques but for whatever reason, IA is common in Europe/Asia and PP in the US. Some people might be allergic to the blood transfusion or react the albumin so it seemed that IA might be safer (unless you were allergic to the product that filtered the blood).
Removing antibodies would be by binding to a target binding molecule. It could be general, but more likely is targeted to a small group of antibody types. One way to do this is to coat the beads in the columns with the target molecule for the antibody in question. It wont work on antibodies for other targets. So this technique would work like Rituximab, but less successfully in general.
I know anything scientific from Alex is correct, so forgive my question, but how does this technique work similarly to Rituximab? Wouldn't the mechanism of Rituximab (killing the B-cells) stop the future production of ALL autoantibodies at the source? How could you make Rituximab only target certain autoantibodies? I am NOT saying you are wrong, I just had never heard of this before and would love to understand it all better.
However by selecting only patients with that specific antibody they increase the response rate.
I don't quite get this part either. If you know that you are studying a specific autoantibody (ies) then wouldn't you WANT to select patients who have those autoantibodies? Otherwise what would be the purpose of the study? Since you can actually measure autoantibodies in the blood, it seems like this kind of study could truly select patients who met the criteria by having the autoantibody (vs. studies with patients with ME/CFS are often critiqued that the patients did not really meet the CCC or ICC criteria etc)? It seems like having the autoantibody is the criteria for the study but would not necessarily change the response rate.
The problem is we do not know how much these antibodies contribute to ME symptoms ... and its only that part of the issue that can be fixed, and even then its temporary.
I totally agree with this but it is a way to study the autoantibodies itself and if treatments like PP or IA are effective. Couldn't this be useful in and of itself?