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Antibody wipeout relieves symptoms of chronic fatigue syndrome (newscientist.com)
135 points by jhartmann on July 6, 2015 | hide | past | favorite | 65 comments



There is considerable support for destroying and recreating immune cell populations to deal with autoimmune diseases and some aging effects. For example, for B cells:

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1) Reversing B cell aging

http://www.impactaging.com/papers/v3/n4/full/100313.html

2) Long-lived autoreactive plasma cells drive persistent autoimmune inflammation.

http://dx.doi.org/10.1038/nrrheum.2011.1

3) B-cell depletion reactivates B lymphopoiesis in the BM and rejuvenates the B lineage in aging

http://dx.doi.org/10.1182/blood-2010-09-307983

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Then for treatment of autoimmune disorders such as MS, more comprehensive destruction:

http://www.eurekalert.org/pub_releases/2009-01/nu-sct012909....

This was also tried for rheumatoid arthritis with mixed results before the development of biologics, and everyone gave up on the immune reboot with chemotherapy in favor of controlling the condition for some patients.

----

Then there are the prospects for destroying T cells specialized to herpesviruses like CMV (you probably have CMV, near everyone has CMV by time old age rolls around, it's very prevalent) that are thought to cause a large degree of immunosenescence by overloading the repertoire of immune cells with memory T cells for CMV and the like - too many of those and not enough naive T cells to deal with new threats and cancer surveillance. That isn't a going concern yet, but it certainly could be soon.


Yes the problem with the CMV (and EBV) T cells is too often ignored. Once these T-cells become more than 80% T-cell population your life expectancy is less than a year. You pretty much have leukaemia.

In my opinion we should be testing all people over the age of 65 for CMV and EBV and putting them on anti-herpies virus drugs to suppress the chronic low level viral turnover that is driving this T-cell clonal expansion.


I would really appreciate any references on this.


Have a look at this paper

Cytomegalovirus-seropositivity has a profound influence on the magnitude of major lymphoid subsets within healthy individuals

S Chidrawar, N Khan, W Wei, A McLarnon, N Smith, L Nayak, and P Moss

Clinical & Experimental Immunology 2009 vol. 155 (3) pp. 423-432

http://doi.wiley.com/10.1111/j.1365-2249.2008.03785.x


Thanks!


I am hoping someone can help here because it has been affecting my life every day. I have been extremely fatigued for the past 2.5 years and I've lost so many things due to it. I sleep the majority of every day away. How do I know if this is CFS?

I guess what I'm asking is, where do I start to cross out other possible causes? Considering so many things can cause fatigue.

Thank you


Go see a good doctor that will be thorough in checking all other probably causes of fatigue. You should probably end up seeing a few specialists as well. The major symptom of CFS is post-exertional malaise, meaning you feel worse after sufficient exertion.

While you wait through what may be many months of medical testing before everything is ruled out, you might try an experiment. Exercise usually helps depression, but usually worsens CFS. Try a bit of gentle exercise, and work your way up gradually over time until you can sustain some intensity. If that improves your fatigue, that's good news, it could be depression, and keep up the exercise. If you feel worse, more depressed, confused, fatigued, with trouble concentrating, that could be post-exertional malaise. Try taking it extremely easy for a few months (maybe many months). Don't do anything that feels like you're pushing yourself. If you start to feel better, if your fatigue and mood start to lift, and you are able to concentrate better, then it could be CFS, and keep up the gentle pacing.

Also, if your fatigue came on after a relatively severe viral infection, that would point to CFS as well.


Wow I don't even know how to thank you for this, this is so extremely helpful. Thank you so much!


I have lived with CFS for about six years now. Step one is to see your primary care doctor and rule out all the things they can test you for. That will take a while. I remember hoping I would have MS because then that would at least explain things. :)

Step two, if you have CFS, is to come up with a plan to manage your energy levels and think about how you are going to live your life. For me, not overdoing it is key. You cannot recover like a healthy person, and often each crash makes your baseline even lower.

Step three, think about how you want to try to treat the underlying issue. Since it's not clear what the underlying issue is, there's a lot of paths here. I was conservative and didn't try a lot of experimental things. I worked with Doctor Jose Montoya at Stanford (http://med.stanford.edu/chronicfatiguesyndrome.html) who is an amazing doctor. He's highly recommended if you can make it to Palo Alto. My health has slowly improved over the years and is much better now than it was say 3 years ago.

Best of luck!


Trust me you don't want MS. The only case where that's the "better thing",is when you have to pick between MS and a brain turmor. (Lymphoma can look surprisingly similar in MRI.)


Thank you so much for your help!


I'm not going to downplay how bad it is for you, I was in a similar situation to you a few years ago.

I'm relatively sure it was simply a bit of depression for me, regular exercise and improving my diet basically cleared it all up.

Definately go see your doctor. Nobody on the internet can really help.


Thank you!


Join our small CFS group on Reddit:

http://www.reddit.com/r/cfs/

You will get good help and tips there.

You can also explore the FAQ for some help:

http://www.reddit.com/r/cfs/wiki/index


Go to your doctor and he/she should be able to run tests to rule other illnesses out. If it is CFS, there are many things you can do to improve your situation, and perhaps recover.


There are some common-ish ones (thyroid problems, iron deficiency, etc.) that can really only be evaluated by a doctor. Seeing a professional is highly recommended.


Very interesting! It didn't work for everyone, but it did work for a majority it looks like.

CFS is a pretty nasty condition, so I'm glad they've found something that works. My only concern would be the side effects from Rituxan. It's a well studied drug, but it really knocks down your immune system.


> Very interesting! It didn't work for everyone, but it did work for a majority it looks like.

Given that they didn't know what caused CFS (and without further study they still don't know for sure), they don't necessarily have a reliable test that distinguishes CFS from other things that present with similar symptoms. So it's entirely possible that CFS is an immune disorder, this treatment worked on people with CFS, and the remaining cases didn't actually have CFS. It's also possible that some fraction of those it didn't work on have CFS and the drug is not entirely effective, or that some fraction of those it did "work" on are experiencing a placebo effect or a treatment for a different disease that responds to the same treatment.


CFS, like most "syndromes", isn't really a well understood disease but rather a cluster of related symptoms that might indicate a currently unknown disease should a cause or mechanism be discovered. Are you chronically fatigued and the doctors can't diagnose an understood cause? Must be Chronic Fatigue Syndrome. Did your infant suddenly die and the doctors can't figure out how? Must be Sudden Infant Death Syndrome.

What this indicates is that, for a subset of people who are chronically fatigued for no reason that the doctors can figure out, there might be some kind of underlying autoimmune reaction that responds to this kind of treatment. If the mechanism is better understood and can be diagnosed, tested, and treated, then it's not Chronic Fatigue Syndrome anymore, but rather an actual disease.


The study was uncontrolled, so we don't know how much of that is the placebo effect (which typically is anywhere between 11 and 46% for CFS treatments). It will be interesting to see the results of the upcoming controlled study. A previous controlled study did show positive results, but it was quite small.


"A 150-person study is now under way, and includes a control group."

I'm curious, the latest study which is presumably what triggered this story, involved no control group, yet they mention a smaller study from 2011 which did use a control.

If this really does hint at a breakthrough, why did it take so long to follow up on the first study, and why did this one not use a control group?


From the study at http://journals.plos.org/plosone/article?id=10.1371/journal.... :

"According to protocol for the previous randomized KTS-1-2008 study, patients assigned to the placebo group should be given the opportunity to participate in a new open-label study with rituximab. The protocol for the present study was designed to learn about the therapeutic efficacy of rituximab maintenance treatment, for response rates and response durations. Also, the experiences could form the basis for design of a future randomized, double-blind and placebo-controlled trial."


so, it is possible that some infection is an original cause for the elevated antibody level. It reminds the history of stomach ulcers where bacteria, not the stress, happened to be the primary reason. Matter over mind once again :)


Most cases of CFS seem to start out as a "post-viral syndrome". Basically people get a virus, recover from the virus but are left with ongoing fatigue symptoms. After six months it's declared to be CFS (CFS isn't a specific disease, it just declares that you've been fatigued for over six months).

So yes, I think many people who've had CFS would say it's a no-brainer that it was related to an infection. In my case I got "mono" (or glandular fever as we call it here) and it turned into CFS for about seven years. But in the end I recovered and I've been fine for nearly a decade now.


Pretty much mirrors the experience of one of my family members. She contracted mumps and pneumonia in a fairly short time period, then was left with ongoing fatigue. A year on, she's definitely improving, but doing too much leaves her fatigued for days and she sleeps for 18+ hours some days.

A cure (or even treatments to shorten the recovery time) would be wonderful.


> This would prevent people from getting enough oxygen, explaining their extreme fatigue, but the team caution that their theory is just speculation for now.

Caution, in scientific journalism; sadly, I'm kind of impressed.


This is pretty solid evidence that CFS is not psychosomatic, given the difference in response between the control group and the group that received treatment. In case anyone was still unsure.


I think there's a flaw in your logic here: the fact that a drug that is targeting the immune system helps so much does not invalidate a psychological component in the etiology. It could be upstream (psychological stress could trigger the immune response that leads to CFS), it could be downstream (CFS leads to mental anguish given a patient's deviation from normative life-course, perceived isolation, and the historically-contested nature of the malady), or it could be both.

That said, a psychological / psychosomatic component wouldn't undermine its legitimacy in any way. Thankfully, I think we are entering an era in which psychological aspects of ailments are recognized as critical, beyond the control of the patient (e.g. not reflecting a lack of virtue or wherewithal on their part), and treatable.


Or it could be that what causes CFS also affects brain chemistry in a way that can result in depression. That's where my money is.


I'm in the bio-pyscho-social camp, I believe the three elements work in concert to keep the show going, over stressing all three consistently does seem to correlate with an immune malfunction, and treatments that approach only 1 of the three 'prongs' appear less successful than those that approach all three.


Not really, it actually seems in line with the expected placebo response in CFS (Cho et al., 2005).


I've not read Cho but in 2011 trial none of the control group given placebos experienced relief against most of those given the drug. That seems like not much of a placebo response to me.


The 2011 study was negative in its primary end-point. If you look at the results you'll see that the divergence between active and placebo groups only happened after the researchers unblinded the data at the 3 month point. Although they say that the patients were still blinded until the end, there are still some question marks about the study.


As for any autoimmune disease, have a read up on Naltrexone (Papers that is, not pseudo science blogs and advocacy sites that are generally poorly substantiated)

One on an MS model in mice : http://www.ncbi.nlm.nih.gov/pubmed/25906771



I have a close friend who has chronic fatigue. It is commonly stigmatized as many regard those who are chronically fatigued as lazy, just making excuses.

But my friend is one of the hardest-working, most productive people I have met and is quite wealthy as a result at first of her code, then as a result of her management expertise.

Even so she feels like crap 24/7 and it just won't go away. Nothing helps.

She can be a little hard to get along with, though.


Research tends to show the opposite, that CFS patients tend to be over-active (pre-illness) and have "action-prone" personalities.


Rather than defaulting to drugs for CFS, I would much rather find the core cause of it? Oftentimes it is an infection, stress or even the food we put into our bodies. You would be amazed at how better you can feel and how much more energy you have by simply changing your diet and lifestyle.


Sounds like you found something that works for you. Excellent!

Diet and exercise were certainly where I started. That was seven years ago. Still no joy.

Infections eventually go away. Maybe. Or we treat them with drugs, diet etc. Stress can be reduced, managed, eliminated. We can change the food we put in our bodies.

When nothing works, then what? Keep looking.


I can sympathize, my wife is asleep next to me and I'm sure she will be excited to hear some progress is being made on CFS. CFS isn't a sexy thing to research, it doesn't get a lot of funding, same thing with a lot of other conditions and syndromes. No idea what causes it, but taking x/y/x unrelated medication seems to alleviate the symptoms.


I hope you find some answers. I understand the struggle.


If you reckon you know what the core cause of CFS is and have done some experiments that provide evidence, you should publish that stuff.


I have personally reversed CFS & an auto-immune disease with crazy high anti-bodies by sticking with a very strict diet and changing life-style.


What is your diet?



Sounds like you did something and then you got better. Sadly, post hoc ergo propter hoc is not a treatment modality.


[flagged]


Please don't be rude.

I think the issue is figuring out the correct "lifestyle" treatment, as that word is quite broad. Research shows that an abnormally low HPA axis is associated with CFS, and in my case what worked was doing things to reverse this. This appears to be the case for other patients who have recovered.


I responded to rudeness with rudeness. Perhaps not constructive but my knee jerk reaction.

I don't have CFS but I can imagine they get an endless barrage of unsolicited comments such as "you need to eat more/less protein/carbs/fat/meat/vegetables/gluten/preserves/alcohol/fad-of-the-month and you'll be cured." I'm sure that people suffering from something as terrible and debilitating as CFS has tried all of that and more. Its the holier-than-thou attitude that gets under my skin.

We know (in general) humans can both survive and thrive on a wide variety of diets.

Sharing your personal experiences and what worked for you is helpful. Writing off research in medication with "why? you just need to change your diet" is not. Especially to those still suffering. It discounts real people who are really suffering and are still looking for answers.


I was by no means intending to be rude. Simply suggesting an alternative solution. I apologize that you took it as me being rude.


I have personally reversed CFS & an auto-immune disease with crazy high anti-bodies by sticking with a very strict diet and changing my life-style. Only after being directed into many black-holes by multiple doctors telling me nothing was wrong or trying to prescribe me anti-anxiety drugs.

So yeah I guess I am a jackass!


Well, probably you did. Or you might have just been sick for a year or two and coincidentally gotten better at the same time as the diet and lifestyle changes. The odds are small, but given that you're a sample size of one it might well prove it to you, but not to others.


I was sick for a long-time and was getting progressively worse. I understand that what works for me may not work for others. I am simply suggesting we look for the root cause and possibly look for alternatives other than drugs. For some people there may be no alternatives and I understand that.


What was the diet?


I was on the autoimmune protocol for about a year and slowly introduced things after that. The first month on the diet sucked. I felt worse. After that though, things really started to turn around. I was also on vit supplements due to a lot of my levels being extremely low (Vit D & Iron) and am still supplementing because my body has a hard time holding onto these things.

I also take a 20 min fast walk each morning when I wake up and do my best to eliminate stress (I know easier said than done).

I had very high antibodies and now have none. I wasn't able to make it past 1pm without crashing and now have no problems making it through the day.

3 years later I am still on a strict diet but not nearly as strict as it once was. There are certain foods that still make me crash (sugar, beer, etc) but overall I got my life back :)

I am not saying this will work for everyone but it has worked for me and others like me.


> I had very high antibodies and now have none.

No you don't.


Okay??


If you had no antibodies you'd be dead. We can test for specific ones, but "very high antibodies" could describe any number of different test results, some of which would clear up on their own in time.

If doctors tried giving you anti-anxiety meds, strict lifestyle and diet changes could well help with some anxiety-causing disorders.

In short, I'm a little skeptical that you've got the correlation/causation correct.


I have Hashimoto's which is an autoimmune disease. My TPO antibodies were very high. Took 3 years to get them in check. Another doctor tried giving me anxiety drugs because he had no idea what was wrong with me and that was his answer. Thankfully I found a great doctor that specializes in autoimmune diseases who put me on the right path.


Yes, I am curious too. The reason for my curiosity is I have been successful via diet as well, so it's to see if we're doing the same thing.


See my comment above. I would love to hear about what you have done too.


In a nutshell, non-fat (or very low fat) vegan. A good resource for this is drmcdougall.com. Though I find McDougall a bit off-putting with his style, IMHO he's on the money, and the diet is what my doctor recommends.

See, this is what makes diet suggestions so difficult. I think this is practically the opposite of what you did.


Interesting. I agree, different diets work for different situations & people. I think sometimes its a lot of trial and error. I am happy your diet is working for you. I plan to do some reading up on it.


You can share your experiences in a helpful way without being condescending. You were condescending.


People do sometimes post comments that seem condescending, but that doesn't make it ok to be mean. Instead, please follow the HN guidelines. The rule here is to post civilly and substantively, or not at all.

https://news.ycombinator.com/newsguidelines.html


Sorry you feel that way. That was not my intention.




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