CDC: CFS not subject to opportunistic infections?!

[alex3619]

Anecdotally its been reported the inconsistent NK function tests have been resolved. They are largely an artifact of the testing process. There are two different broad testing methodologies. One consistently shows no NK cell dysfunction. The other the opposite. Isolated NK cells test fine. NK cells in serum test as dysfunctional. This HAS NOT BEEN FORMALLY PUBLISHED though, and may require a study demonstrating this before it will be widely accepted.

Taking this interpretation, some factor is blocking NK function. It could even be B cell related - in which case Rituxmab may even restore NK cell function. This is still speculation of course.

 

[NK17]

With all due respect to her work and your opinion @Jonathan Edwards, Prof. Julia Newton is not an immunologist. She is doing an amazing job on the autonomic dysfunction and muscle problems, but again she is not testing for immune dysfunction nor for specific pathogens.

We tend to forget that we can't look at the forest if we study one single tree, we'll miss the clues that have been talking to us.

Doctors such as Daniel Peterson, Dharam Ablashi, José Montoya, Nancy Klimas, Nicoletta Carlo-Stella, Sonia Marshall Gradisnik and Andreas Kogelnik, just to name a few and in historical order, can't be all wrong about infectious agents' participation in the clinical realm of ME.

I'm also very curious about Dr. Amolak Bansal work on ME patients immunological profiles and would love to hear more about his findings .

 

[Hip]

Anecdotally its been reported the inconsistent NK function tests have been resolved. They are largely an artifact of the testing process. There are two different broad testing methodologies. One consistently shows no NK cell dysfunction. The other the opposite. Isolated NK cells test fine. NK cells in serum test as dysfunctional. This HAS NOT BEEN FORMALLY PUBLISHED though, and may require a study demonstrating this before it will be widely accepted.

I don't know if it's what you are referring to, Alex, but in this table (Table 1) of this study (by Nancy Klimas et al) on the NK cell function of ME/CFS patients, they compared the results of different NK testing techniques (they compared CD26 on cells, and CD26 in serum).

It's also interesting that the natural killer cell cytotoxicity (NKCC) results in that table seems to be able to distinguish ME/CFS patients from healthy controls with almost 100% accuracy, if I have read Table 1 correctly, since ME/CFS patients had NKCC% values in the range 8–21, and healthy controls in the range 20–37.

 

[Hip]

How do we know the tests are not reliable?

I think it's well known that Chlamydia pneumoniae testing is not very reliable (see this article). And this article states that CDC-approved Lyme tests are just over 90% accurate.

 

[alex3619]

I don't know if it's what you are referring to, Alex, but in this table (Table 1) of this study (by Nancy Klimas et al) on the NK cell function of ME/CFS patients, they compared the results of different NK testing techniques (they compared CD26 on cells, and CD26 in serum).

It's also interesting that the natural killer cell cytotoxicity (NKCC) results in that table seems to be able to distinguish ME/CFS patients from healthy controls with almost 100% accuracy, if I have read Table 1 correctly, since ME/CFS patients had NKCC% values in the range 8–21, and healthy controls in the range 20–37.

Actually I was referring to something on a recent Simmaron (Cort?) blog, where Klimas got together with others who routinely find no problems and found and resolved the issue. This is however a comment on a blog, not a published paper. If accurate, it means that the researchers knocking heads together resolved the issue. It still has to be demonstrated in a published study.

 

[IreneF]

I used to think I had stopped getting the ordinary runs of colds and flu-like conditions, but then I wondered if it was just because I stayed in the house all the time and just wasn't exposed to many people. Then I had rituximab, and really the only side effect was a couple of thoroughly unpleasant colds. Really the worst I've had since my kids were little, and I was staying away from strangers and practicing extra-good hygiene.

Now I am back to "normal" and my son has a cold. I accidentally shared some of his food before he told me he felt sick. For the past couple of days I've been in a bit of a crash, but he's got the fever, the red eyes, the cough, the sore throat, the runny nose . . . . I feel like I'm fighting it but not mounting the full-bore response. It would be interesting to see what differences there are between my son and myself.

I've also had high titers for Mycoplasma pneumoniae, but it's been completely asymptomatic.

The only other strange infection/non-infection I got was a series of sinus infections. I think those were due to some kind of allergy or inflammation, because I've completely avoided them by taking a daily antihistamine.

Dr. Montoya's people found that patients' cytokine levels, and esp. leptin levels, varied depending on how long they had the disease. I don't know if this has been published, but his presentation should still be available on the Stanford site. This would explain some of the contradictory findings or seemingly-unreliable tests.

 

[WillowJ]

hi Dr. Edwards,

Here is a paper of Dr. Gwen Kennedy's that I find intriguing:
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC1770396/
One of her possible explanations is a chronic or reactivating infection, though another is "an abnormal host response to noxious stimuli". Is that quote in line with what you are thinking as far as autoimmune response?

Here's a newer one that I don't think I've read the full text of:
http://www.ncbi.nlm.nih.gov/pubmed/20819963

I haven't seen any other group attempt to replicate this finding.

Do you think this test could be useful?

ETA: sorry, this may be OT for this thread

 

[NK17]

I don't know if it's what you are referring to, Alex, but in this table (Table 1) of this study (by Nancy Klimas et al) on the NK cell function of ME/CFS patients, they compared the results of different NK testing techniques (they compared CD26 on cells, and CD26 in serum).

It's also interesting that the natural killer cell cytotoxicity (NKCC) results in that table seems to be able to distinguish ME/CFS patients from healthy controls with almost 100% accuracy, if I have read Table 1 correctly, since ME/CFS patients had NKCC% values in the range 8–21, and healthy controls in the range 20–37.

Absolute spot on find regarding NKCC in PWME @Hip!
Dr. Mary Ann Fletcher Ph.D is one of the authors of the study, she works closely with Nancy Klimas, her specialty is immunology.
She's a great researcher and a strong advocate for PWME.

 

[Jonathan Edwards]

OK, so there seems to be some sort of consensus that ME/CFS is not specifically and consistently an immunodeficiency state and that it is not associated with opportunistic infection in the strict sense, which is where we started out.

I am very ready to believe that individuals with ME have immune abnormalities but I am still not convinced there is sufficiently well documented and reproduced evidence for known abnormalities in even subsets. I discussed with the Norwegian physicians about immunological clues in their patients and they basically said that their patients appeared to be uniformly immunologically normal. High and low lymphocyte subset numbers and immunoglobulin levels are common enough in healthy people so it is hard to know whether they are actually related to disease in PWME. Autoantibodies might be more common but it is very hard to pin that down.

I will continue to keep my eyes and ears open.

 

[Jonathan Edwards]

Anecdotally its been reported the inconsistent NK function tests have been resolved.

Yes, I see that his has been proposed, but as you say, there does not seem to be published confirmation that this is really the explanation.

 

[Jonathan Edwards]

With all due respect to her work and your opinion, Prof. Julia Newton is not an immunologist. She is doing an amazing job on the autonomic dysfunction and muscle problems, but again she is not testing for immune dysfunction nor for specific pathogens.

I don't think I buy that NK17. Julia Newton's group has taken an ME cohort and studied a wide range of issues, including psychiatric profiles, hypothalamic-pituitary issues, muscle function and microarray analysis relevant to immune function alongside a Sjögren's cohort. She works with an impressive range of physicians in different disciplines. She is working in conjunction with two rituximab projects in immune disorders. She may not be doing NK assays but that may be because, like me, she is not sure what they mean and they are notoriously difficult to get consistent. Several practicing physicians are involved with the patients and they are not going to miss significant infections.

Doctors such as Daniel Peterson, Dharam Ablashi, José Montoya, Nancy Klimas, Nicoletta Carlo-Stella, Sonia Marshall Gradisnik and Andreas Kogelnik, just to name a few and in historical order, can't be all wrong about infectious agents' participation in the clinical realm of ME.

Why not? Everybody being wrong about disease mechanisms is a standard situation. Everybody was wrong about peptic ulcer. Everybody was wrong about T cells in RA. Everybody was wrong about cholera. Everybody was wrong about lung cancer. Until somebody found out the real answer. Why is Dr Kogelnik using rituximab if he thinks ME is an immunodeficiency state? Why is Dr Montoya suggesting that valcyte may be working as an immunomodulator? I think some of these people have already moved on significantly.

 

[A.B.]

Why not? Everybody being wrong about disease mechanisms is a standard situation. Everybody was wrong about peptic ulcer. Everybody was wrong about T cells in RA. Everybody was wrong about cholera. Everybody was wrong about lung cancer. Until somebody found out the real answer. Why is Dr Kogelnik using rituximab if he thinks ME is an immunodeficiency state? Why is Dr Montoya suggesting that valcyte may be working as an immunomodulator? I think some of these people have already moved on significantly.

I'll repeat my suggestion to contact Dr Meirleir. I remember reading one of his presentations, which I cannot find at the moment, in which he claimed that some patients do have ongoing infection and get subjectively and objectively better with antibiotics or antivirals. The claim that infection plays a role in a subset of patients does seem to be supported by objective tests.

Even though this forum has some knowledgeable users, this is really a discussion that you should have with one of the experts who approaches the illness from this angle. We patients can only contribute so much (maybe someone will remember which presentation I'm referring to).

 

[Seven7]

@Hip do you mean CD56 instead of Cd26??? I go there and that is what I am tested as NK = CD56.

 

[Jonathan Edwards]

I'll repeat my suggestion to contact Dr Meirleir. I remember reading one of his presentations, which I cannot find at the moment, in which he claimed that some patients do have ongoing infection and get subjectively and objectively better with antibiotics or antivirals. The claim that infection plays a role in a subset of patients does seem to be supported by objective tests.

Yes, I am familiar with those sorts of presentations. I spend hours looking at videos of old conference presentations. I judge the quality of the content in the way that I would do for material presented at an American College of Rheumatology meeting - surely I should be as rigorous for ME as I am for RA or lupus? I remain unconvinced. And I am not out on a limb there. The majority of people I meet in the ME research world are of the same opinion. So far we only have theories, nothing hard to go on.

The problem that I see is that although it may be coming there is not yet a consensus in the research meeting circuit that data on ME should be scrutinised in the way that is considered mandatory at a Rheumatology meeting. The reason why I raise this on PR rather than talking to the (maybe rather few) researchers I have yet to meet personally is that I see PR as a potential force for moving the agenda towards this more rigorous approach. Charities run by patients or carers are making a lot of the running in getting scientists to get there act together. There is nothing unusual about that either. Research into arthritis was driven by charities for decades and still is to a large extent. PR is not quite like a funding charity but it is a talking shop that can put pressure on people to publish rigorous studies on which we can build, rather than anecdotal observations that leave us wading through a treacle of uncertainty.

 

[NK17]

I don't think I buy that NK17. Julia Newton's group has taken an ME cohort and studied a wide range of issues, including psychiatric profiles, hypothalamic-pituitary issues, muscle function and microarray analysis relevant to immune function alongside a Sjögren's cohort. She works with an impressive range of physicians in different disciplines. She is working in conjunction with two rituximab projects in immune disorders. She may not be doing NK assays but that may be because, like me, she is not sure what they mean and they are notoriously difficult to get consistent. Several practicing physicians are involved with the patients and they are not going to miss significant infections.




Why not? Everybody being wrong about disease mechanisms is a standard situation. Everybody was wrong about peptic ulcer. Everybody was wrong about T cells in RA. Everybody was wrong about cholera. Everybody was wrong about lung cancer. Until somebody found out the real answer. Why is Dr Kogelnik using rituximab if he thinks ME is an immunodeficiency state? Why is Dr Montoya suggesting that valcyte may be working as an immunomodulator? I think some of these people have already moved on significantly.

Yes Jonathan Edwards, you may be right about all this doctors getting it wrong, it has happened many many times before in the past, the peptic ulcers which were thought to be caused by stress and spicy food are the classic example. We can thank Dr. Barry Marshall for infecting himself with Helicobacter Pylori to prove his hypothesis. We can also think about Harald Zur Hausen who for more than 30 years was disbelieved when presenting evidence of a causal link between certain strains of HPV and cervical cancer. Now we have vaccines to prevent cervical cancer. Both doctors have been awarded a Nobel Prize for these seminal discoveries.
And I should not forget what you and Jo Cambridge had to go through to prove B cells involvement in RA.
To go back to the ME field, my instinct tells me that all our doctors and researchers hold a piece of the puzzle. This is the typical elephant in the room situation. Dr. Peterson might hold the head and Dr. Julia Newton might hold the tail . What 's important is that we are all working together to solve this complicated puzzle. A puzzle that is much more complex than discovering what causes ulcers and cervical cancer.
I think that Fluge and Mella are on the launching ramp to big recognition and a real bright future for all PWME and I see you as a solid old bridge between the old continent and the now not so new world. Everything you bring on the table, wether here on PR or amongst your colleagues is truly important and I can't stop thanking you for that.

You stand correct about Julia Newton's group, my post was written in the wee hours of the day, aches and pains tend to make you forget what you've read. Dr. Newton's work on PBC and Sjogren's and now ME, gives her an edge in understanding what I think she calls fatiguing illnesses.

 

[alex3619]

Yes, I see that his has been proposed, but as you say, there does not seem to be published confirmation that this is really the explanation.

There is a second problem though. Even if NK dysfunction is proven, we have no idea as to whether or not it is clinically important. There is a distinct lack of data that boosting NK function improves symptoms.

 

[heapsreal]

There is a second problem though. Even if NK dysfunction is proven, we have no idea as to whether or not it is clinically important. There is a distinct lack of data that boosting NK function improves symptoms.

They need to find something that reliably increases nk function in cfs/me patients first and then trial it. Some may also increase nk numbers or nk function but again it might need to be more specific to increasing nk bright cell function. Best would be to increase numbers and function/bright cell function to normal range to see if symptoms improve. It could take time for nk cells to clear infections also.

It might end up being just a marker but i struggle with that idea when one looks at the job of the nk cell?

 

[Hip]

I've tried NK cell activation-boosting supplements for short periods of a month or so, and I found I felt a bit better after a few days taking them, but nothing spectacular. There are a number of supplements that increase NK cell activation very substantially (eg: transfer factor, MGN3, AHCC, cordyceps), so if they were the magic bullet for ME/CFS, I am sure we would have heard it by now.

Though NK cell boosters might be useful for those ME/CFS patients that keep picking up colds, etc. @justy

 

[heapsreal]

I've tried NK cell activation-boosting supplements for short periods of a month or so, and I found I felt a bit better after a few days taking them, but nothing spectacular. There are a number of supplements that increase NK cell activation very substantially (eg: transfer factor, MGN3, AHCC, cordyceps), so if they were the magic bullet for ME/CFS, I am sure we would have heard it by now.

Though NK cell boosters might be useful for those ME/CFS patients that keep picking up colds, etc. @justy

I think it needs to be a long term thing and also i think a tolerance develops to the immune stimulation of these substances, i think maybe we need several to alternate between.

I also dont think these are probably strong enough on their own but maybe say after treat certain infections etc eg good improvement with antivirals then maybe using these nk boosters in an alternating pattern could be enough to keep some infections down.

Also could benefit people who have been on say interferon for EV, relapses are common from what dr chia says, maybe switching to these immune boosters/interferon inducers is a way to keep the benefits of this therapy longer??

 

[justy]

Hi,
I was just laying in bed this morning, as you do, worrying about various things when my mind wandered to this discussion and what it wondered was whether @Jonathan Edwards might be able to say if he can see what mechanism would be at play in the group of us who do catch everything going and then can't clear things quickly like our healthy family members do.

There is a large group of us around who have this problem of, lets say, common everyday infections/illnesses being more frequent, severe and prolonged than they are in the people around us. I know this is anecdotal, but I have met many patients with this profile.

We also seem to have a preponderance of stomach bugs, and upper and lower respiratory tract infections as the main problems. I have had one after the other without a break since early June this year and it has severely affected my overall functioning and caused a serious decline in my M.E. I now almost completely rely on a wheelchair for getting out and about and once again even conversations can be exhausting.

I understand that we do not en masse have testable, normal immune dysfunction, as observed by Fluge and Mella in your conversations with them. In this case could you try to imagine what could logically cause this state of affairs?

All the best
Justy.