Chronic fatigue syndrome and fibromyalgia following immunization with the hepatitis B vaccine

[Hip]

An interesting video by autoimmunity researcher and clinician Dr Yehuda Shoenfeld, discussing the effect of adjuvants in vaccines on autoimmunity:

▶ Vaccine Safety Conference Session 13 - Dr. Yehuda Shoenfeld, MD, FRCP - YouTube



Some video highlights (with timecodes):

26:00 Animals inoculated with just adjuvants (and without any antigens) developed manifestations of autoimmune disease.

26:20 Adjuvants are quite common in nature: mineral oil material can be found in canned foods.

28:34 The evidence that vaccines can cause rheumatological diseases.

37:30 The mechanisms by which vaccines induce autoimmunity.

38:00 The only one vaccine that has never been linked to triggering any autoimmune disease is Pneumovax, and this also happens to be the only vaccine that does not contain any adjuvants.

43:27 Fatigue symptoms and CNS involvement: due to nano-particles of aluminum that enter the brain?

 

[natasa778]

this may be of interest

...DCs connect the innate and adaptive immune responses,since the activation state of the DC determines the type of immune response that gets triggered. Although it is evident that innate immune receptors on DCs are required for optimal immune activation, the mechanisms by which these receptors regulate the functioning of DC have not yet been fully revealed. What is clear is that, in response to a variety of stimuli, DCs change from immature cells specialized for antigen capture into mature cells specialized for T cell stimulation.Thus a fundamental question is how the signaling network downstream of TLRs, NLRs and other innate immunity receptors regulate DCs,and hence, activatesthe types of T cell responses required to fight infections.

My introduction to immunology was through vaccine adjuvants- immunologist’s “dirty little secret”. While working on my PhD project I found that, after taking in aluminum adjuvants, DCs induce T cell differentiation into Th2 cells in a caspase-1-dependent manner (1). At the same time, caspase-1 activation by aluminum adjuvants is critically dependent on an intracellular innate immune signaling system called the NLRP3 inflammasome. This work established a good example of a connection between innate and adaptive immunity through DCsand got me interested in vaccine development and adjuvant function of innate immune ligands.

My research on adjuvantslead me to study how innate immune receptors regulate the specific functions of DCs, and how transcriptional and local post-translational modifications induced by innate immune signals in these phagocytes sculpt appropriate T cell responses....

http://www.massgeneral.org/children/about/newsarticle.aspx?id=4137

 

[charles shepherd]

Chronic fatigue syndrome and fibromyalgia following immunization with the hepatitis B vaccine: another angle of the 'autoimmune (auto-inflammatory) syndrome induced by adjuvants' (ASIA).
Agmon-Levin N, Zafrir Y, Kivity S, Balofsky A, Amital H, Shoenfeld Y.
Immunol Res. 2014 Nov 27. [Epub ahead of print]
DOI 10.1007/s12026-014-8604-2
http://www.ncbi.nlm.nih.gov/pubmed/25427994/
http://link.springer.com/article/10.1007/s12026-014-8604-2

I continue to receive reports from people, often health workers, who clearly predate the onset of their ME/CFS to one or more doses of hepatitis B vaccine
The number of people reporting an onset of ME/CFS following hepatatis B vaccine, when compared to other vaccines, seems to be disproportionate the use of this vaccine in the population - which is interesting to say the least
And some of patients I have seen in this situation have unusual neurological symptoms/signs that are not characteristic of ME/CFS
So I remain convinced that there is something unusual happening here
This is the updated basic information that I currently provide to queries about hepatitis B vaccine and ME/CFS:


Anecdotal evidence indicates that a number of vaccinations are occasionally capable of either triggering ME/CFS, or causing an exacerbation of pre-existing symptoms, and the CMO Working Group report acknowledged (in section 3.3.2) that vaccinations can occasionally act as a trigger factor in the development of ME/CFS

The link is biologically plausible but there hasn't been any really robust research carried out to investigate the role of vaccinations as immune system stressors in the causation of ME/CFS

Two fairly recent published reports of interest relate to an MHRA review of HPV vaccine (Cervarix) and ME/CFS >>

http://www.mhra.gov.uk/NewsCentre/Pressreleases/CON316330

and two case reports re Swine Flu vaccine and ME/CFS:

http://www.meassociation.org.uk/201...accination-bmj-rapid-responses-21-march-2014/

I have a longstanding interest in the role of vaccinations in ME/CFS and my patient evidence on the subject, which is now quite substantial (especially in relation to a link with hepatitis B vaccines) and includes a number of health workers who were vaccinated almost as a condition of employment, indicates that hepatatis B vaccine appears to play an unusual and significant role here, possibly (as has been postulated in the past) because some of these vaccines are highly immunogenic:

http://www.ncbi.nlm.nih.gov/pubmed/9651632

This is supported by the results of the MEA website poll on the roll of vaccinations as trigger factors for ME/CFS:

MEA WEBSITE POLL:

• 
  If your ME/CFS was triggered by a vaccination, which vaccine was involved?
  
  • Hepatitis B (57%, 338 Votes)
    
    
  • Flu (9%, 51 Votes)
    
    
  • Other (7%, 41 Votes)
    
    
  • BCG (6%, 33 Votes)
    
    
  • Cannot remember (5%, 31 Votes)
    
    
  • Combination (5%, 27 Votes)
    
    
  • Tetanus (3%, 18 Votes)
    
    
  • Meningitis (3%, 17 Votes)
    
    
  • MMR (2%, 14 Votes)
    
    
  • Polio (2%, 10 Votes)
    
    
  • Hepatitis A (1%, 7 Votes)
    
    
  • Typhoid (0%, 4 Votes)
    
    
    Total Voters: 591
    

Start Date: April 30, 2010 @ 3:20 pm
End Date: June 2, 2010 @ 3:20 pm

 

[natasa778]

NLRP3 variations have been proposed to play a role in susceptibility to chronic inflammation
(again lists aluminum, silica etc as activators, in addition to pathogens, page 22)

NLRP3 found activated in fibromyalgia in this one study

These results show an important role for the NLRP3 inflammasome in the pathogenesis of FM, and the capacity of CoQ10 in the control of inflammasome.

 

[natasa778]

More from the post-doc profile page I posted earlier:

...Our ultimate goal is to understand how the network of innate immune receptors shapes T cell differentiation and the development of adaptive immunity using DCs as a critical control point connecting innate and adaptive systems. Knowing these mechanisms will allow us to understand how DCs sense pathogens and structure their response to drive appropriate T cell activation and how pathogens by manipulating DC maturation divert away from protective adaptive immunity.It will provide better insight into how PRRs regulate antigen processing and priming of naïve T cell responses to pathogens. Additionally, it will help identify specific molecular targets that can aid rational vaccine design and development of adjuvants tailored to drive specific immune responses.

 

[Mij]

I had a series of vaccinations one month after my intial onset. I was functioning ok until I had the series of Hep B vaccines, that's when the odd fatigue started and my anti-thyroid antibodies shot up.

 

[barbc56]

This is supported by the results of the MEA website poll on the roll of vaccinations as trigger factors for ME/CFS:

What you state may be true. However, patient surveys are often misleading.

Thanks.
Barb

ETA I see you used the word suggest. My foggy mind processed the word as causes, which has a different connotation.

 

[Jonathan Edwards]

I continue to receive reports from people, often health workers, who clearly predate the onset of their ME/CFS to one or more doses of hepatitis B vaccine

I agree that this is worth further study but I think we need a formal epidemiological approach in an unbiased population. My worry is that Hep B vaccination is given in very different life circumstances from most other vaccinations. Most of the others are given to children or the elderly (flu). Moreover, both flu and tetanus vaccine are perceived as 'routine' and may easily be forgotten. Hep B is something of an event because it is associated with getting a new job, risks, uncertainties etc. I remember my Hep B vaccinations forty years later but have no idea when I last had tetanus.

I nevertheless agree that a link to ME/CFS is very plausible. What may be less clear is whether this has anything to do with autoimmunity or something called 'ASIA'.

 

[Snow Leopard]

And some of patients I have seen in this situation have unusual neurological symptoms/signs that are not characteristic of ME/CFS
So I remain convinced that there is something unusual happening here

Hi, I am really curious as to what unusual neurological symptoms/signs you have seen in this subset of patients?

 

[Hip]

The number of people reporting an onset of ME/CFS following hepatatis B vaccine, when compared to other vaccines, seems to be disproportionate the use of this vaccine in the population - which is interesting to say the least

That is very interesting. Hep B vaccine is given to health workers and a few other groups, which constitute a small percentage of the population (whereas most of the other vaccinations on the list are given to nearly everybody). And yet in your poll, 57% of all ME/CFS cases that arise after vaccination are from the hepatitis B vaccine, indicating that this may be a far more potent inducer of ME/CFS than the other vaccines.

Though as Jonathan Edwards says, in the UK at least, hepatitis B vaccine is only given to adults, whereas the other vaccines are all given to children. Though in the US, as of 1994 the hepatitis B vaccine is now on the childhood vaccine schedule.

Recently the Federal US Court ruled that hepatitis B vaccine caused ME/CFS in one patient, and awarded the patient $1.1 million.

How do you know that the immune system only reacts to the pathogen antigens in the vaccine? Maybe it reacts to all other ingredients as well. Some vaccines are manufactured with yeast. If the vaccine still containd traces of yeast, is the person also getting vaccinated against yeast? This might lead inflammation of the intestine since yeast is part of the microbiome. Other vaccines are manufactured using human cell lines, or egg proteins. What about the nutrients the culture needs: can vaccines cause immune reactions against certain nutrients?

Anyway, I have wondered what's different about the Hepatitis B vaccine (it might be a particular product, ingredient or method of production that causes problems).

Interestingly enough, if you look at this website listing vaccine ingredients, the only two vaccines on the list that are manufactured from yeast are the hepatitis B vaccine, and the Gardasil HPV vaccine (but not the Cervarix HPV vaccine), and there are anecdotal reports of ME/CFS arising after HPV vaccination, as well as a strong association of ME/CFS with hepatitis B vaccination.

The website says that yeast protein is definitely present in the hepatitis B vaccine. Might this yeast protein act as an additional immunostimulatory adjuvant in the vaccine, thus further increasing the risk of precipitating autoimmunity? This paper found that yeast glucan acts as an adjuvant.

 

[Snow Leopard]

My personal opinon is that, the risk is analogous to that of Guillain barre syndrome, which is associated with vaccination, but is more common after viral infection, than vaccination.

The adjuvants aren't necessarily doing anything special, other than vigorously stimulating the immune system, which is why they are added in the first place.

But it still begs the question - what is special about those viruses (EBV) or vaccinations (Hep B) that are more likely to trigger the illness? We know that EBV has several proteins that manipulate the immune system in interesting ways. Perhaps we should start looking at those pathways as a clue?

 

[Hip]

My personal opinon is that, the risk is analogous to that of Guillain barre syndrome, which is associated with vaccination, but is more common after viral infection, than vaccination.

Dr Chia, who tends to thoroughly investigate the medical history of his patients, found that around 1.5% of ME/CFS patients appeared to have their disease triggered by vaccination.


Though it is possible there may be a difference in the nature of the ME/CFS triggered by vaccines, compared to ME/CFS triggered by infectious pathogens.

Assuming Dr Yehuda Shoenfeld's ideas on vaccine adjuvants precipitating autoimmunity are along the right lines, then vaccine-triggered ME/CFS may be autoimmune in character, perhaps corresponding, in Jonathan Edwards's classification of possible ME subtypes, to one of the autoimmune subtypes, such as ME1.

Whereas infectious pathogen-triggered ME/CFS may have a different etiological basis: this subset seems primarily driven by the continued presence of the pathogen in the body, in that evidence indicates if you decrease levels of the infectious pathogen in the ME/CFS patient, then the ME/CFS symptoms will abate correspondingly. This happens in parvovirus B19-caused ME/CFS: when you use IV immunoglobulin as an antiviral and decrease parvovirus loads, the patient goes into remission. And in Dr Chia's research using IV interferon and oxymatrine on enterovirus-associated ME/CFS, a reduction or remission of ME/CFS symptoms corresponds to a reduction of enterovirus loads in the stomach tissues (as measured via stomach biopsy).


In autoimmune process (not that I know very much about them), once a trigger has kicked off an autoimmune state, it seems that even if you remove the trigger the autoimmune condition still remains. Obviously this connected to the memory cells of the immune system. If I understand it correctly, this generally means that an autoimmune disease, once triggered, will persist for the rest the patient's life.



It would certainly be interesting to try to characterize the symptomatology, lab tests, and prognosis of suspected vaccine-triggered ME/CFS, and compare it to pathogen-triggered ME/CFS.

 

[natasa778]

Though as Jonathan Edwards says, in the UK at least, hepatitis B vaccine is only given to adults, whereas the other vaccines are all given to children. Though in the US, as of 1994 the hepatitis B vaccine is now on the childhood vaccine schedule.

It is given to newborns isn't it? If any of those babies went on to develop ME or similar neurological issues how would those could possibly manifest in a one-year old? What surface symptoms would one expect to observe?

 

[natasa778]

An interesting video by autoimmunity researcher and clinician Dr Yehuda Shoenfeld, discussing the effect of adjuvants in vaccines on autoimmunity:

▶ Vaccine Safety Conference Session 13 - Dr. Yehuda Shoenfeld, MD, FRCP - YouTube

Some video highlights (with timecodes):

26:00 Animals inoculated with just adjuvants (and without any antigens) developed manifestations of autoimmune disease.

If that is true than quite a finding!

Some of these talks sound interesting, but unfortunatly no links or slides

3rd International Symposium on Vaccines - Everything you wanted to know about vaccines and autoimmunity in one symposium: http://www2.kenes.com/Autoimmunity/Scientific/Pages/3rdInternationalSymposiumonVaccines.aspx

 

[Hip]

3rd International Symposium on Vaccines - Everything you wanted to know about vaccines and autoimmunity in one symposium: http://www2.kenes.com/Autoimmunity/Scientific/Pages/3rdInternationalSymposiumonVaccines.aspx

Looks like a very interesting set of presentations.

 

[natasa778]

Looks like a very interesting set of presentations.

Here is a recent paper by Shoenfeld, possibly what was presented there:
Immunization with hepatitis B vaccine accelerates SLE-like disease in a murine model

Alum, an aluminum-based adjuvant, induces Sjögren's syndrome-like disorder in mice.

And this, very interesting
Autoimmune/autoinflammatory syndrome induced by adjuvants (ASIA syndrome) in commercial sheep http://www.ncbi.nlm.nih.gov/pubmed/23579772

We describe a form of the autoimmune/autoinflammatory syndrome induced by adjuvants (ASIA syndrome) in commercial sheep, linked to the repetitive inoculation of aluminum-containing adjuvants through vaccination. The syndrome shows an acute phase that affects less than 0.5% of animals in a given herd, it appears 2-6 days after an adjuvant-containing inoculation and it is characterized by an acute neurological episode with low response to external stimuli and acute meningoencephalitis, most animals apparently recovering afterward. The chronic phase is seen in a higher proportion of flocks, it can follow the acute phase, and it is triggered by external stimuli, mostly low temperatures. The chronic phase begins with an excitatory phase, followed by weakness, extreme cachexia, tetraplegia and death. Gross lesions are related to a cachectic process with muscular atrophy, and microscopic lesions are mostly linked to a neurodegenerative process in both dorsal and ventral column of the gray matter of the spinal cord. Experimental reproduction of ovine ASIA in a small group of repeatedly vaccinated animals was successful...

full paper unfortunately behind a paywall

 

[Snow Leopard]

Whereas infectious pathogen-triggered ME/CFS may have a different etiological basis: this subset seems primarily driven by the continued presence of the pathogen in the body, in that evidence indicates if you decrease levels of the infectious pathogen in the ME/CFS patient, then the ME/CFS symptoms will abate correspondingly.

This has always been an interesting hypothesis, but seems to be increasingly difficult to prove...

 

[Hip]

This has always been an interesting hypothesis, but seems to be increasingly difficult to prove...

It's not difficult to show an association between lowered blood or tissue levels of ME/CFS-triggering pathogens and improvement or remission of ME/CFS symptoms. As mentioned, this association can be easily demonstrated for enterovirus and parvovirus. Of course, that association does not definitively prove that the pathogen was causing the symptoms, but it's not hard to convince yourself that this is likely the case, given that we know all sorts of infections can precipitate sickness behavior symptoms (which are very similar to ME/CFS symptoms).

 

[Hip]

In addition to immune stimulation from vaccine adjuvants being linked to the triggering of autoimmunity, it should be noted that certain herbal immunostimulants such as Echinacea and spirulina are also implicated in worsening pre-existing autoimmune conditions, or triggering new ones.

And Dr Chia found that the herbal extract oxymatrine, which is thought to be an immunomodulator, triggered rheumatoid arthritis in a couple of his ME/CFS patients. Chia says that oxymatrine is not advisable for those with autoimmune tendencies.

So it's not just adjuvants; other types of immunostimulants can also trigger autoimmune diseases, it seems.

I wonder if the popularity of immune boosting supplements such as Echinacea and spirulina may be another factor contributing to the increased incidence of autoimmune diseases.


I had a personal experience of an immunostimulant triggering an autoimmune disease: I unfortunately precipitated rheumatoid arthritis in a family member recently, by giving them the immune stimulating supplement methylcobalamin, at a sublingual dose of 10 mg (the equivalent of say a 500 mcg methylcobalamin injection). Within 12 hours of taking this methylcobalamin this family member had terrible pains in the joints; these pains persisted permanently, and were later diagnosed as rheumatoid arthritis, which was treated with RA drugs for a while.

This family member never had any joint problems before, but within 12 hours of taking a high dose of methylcobalamin, the autoimmune condition of rheumatoid arthritis had been triggered. Methylcobalamin stimulates CD8 T cells and natural killer cells.†

This adverse reaction to methylcobalamin I imagine is pretty rare. (And may only occur in those with certain susceptibilities: I read that people with high histamine may have adverse reactions to methylcobalamin, and this family member suffers from high histamine).

But I found it astounding how a one-off immunostimulatory event like this could instantly trigger an autoimmune condition, which then remains for the rest of your life.

 

[melamine]

This adverse reaction to methylcobalamin I imagine is pretty rare. (And may only occur in those with certain susceptibilities: I read that people with high histamine may have adverse reactions to methylcobalamin, and this family member suffers from high histamine).

But I found it astounding how a one-off immunostimulatory event like this could instantly trigger an autoimmune condition, which then remains for the rest of your life.

Very interesting Hip, and of personal interest to me right now for the very reasons you observed. I have autoimmune features and have also been looking at histamine/mast cell disorders as a possible explanation for some of my symptoms. It reminds me a little bit too, of the CNS reactions I've gotten to glutamic acid within 4 hours of ingestion, that then "bloomed" over the next few days and weeks to symptoms that never fully resolved. Although I have a tendency to adverse reaction to certain quantities or formulas of B vitamins and other "energizing" or immune modulating things - they tend to depress my functionality while I feel overstimulated -. I would not have suspected high dose B12 as a potential culprit. A cautionary tale. Thanks for sharing.

Your story reminds me of a bad reaction to Rituximab that I read about recently that left the person paralyzed and wheelchair-bound. I would post it if I could remember where I read it.

As far as symptoms being triggered and remaining for the rest of ones life, it seems to be the nature of the autoimmune response in the same way as some infections.