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» LymeNet Flash » Questions and Discussion » Medical Questions » Auto immune caused by pathogens?

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Author Topic: Auto immune caused by pathogens?
Brussels
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http://www.nature.com/cmi/journal/v8/n3/full/cmi201077a.html

A very interesting scientific article on immune diseases probably caused by infections and how treatments aiming immunosuppression is NOT the way to go.

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Brussels
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Some excerpts

It is now understood that microbial cells vastly outnumber our own human cells, by a factor of at least 10∶1.

......

However, molecular analysis has revealed that nearly all humans acquire multiple persistent viruses within the first years of life, viruses that generally remain with them throughout life.

The amniotic fluid, previously considered completely sterile, was shown to harbor uncultivated, previously uncharacterized taxa of bacteria, the presence of which was robustly correlated with premature birth.


Discrete pathogens such as human herpesvirus-6 (HHV-6), cytomegalovirus, Epstein–Barr virus (EBV) and Chlamydia pneumoniae, have been repeatedly identified in association with autoimmune disease.


...in autoimmune disease, the body is not targeting its own tissues, but is generating antibodies against fragments of these metagenomic communities of microbes.

---
One of the most effective survival mechanisms involves pathogens that enter host cells, especially the phagocytic cells.

Earlier work has demonstrated that intracellular pathogens are indeed present in patients with a variety of autoimmune conditions.

Intracellular microbes living within nucleated cells can interfere with DNA transcription and repair mechanisms, which allows them to create much of the systemic dysfunction often associated with autoimmune diagnoses.

---------------

While high titers of rheumatoid factor (RF) are associated with severe rheumatoid arthritis, they also appear in a number of other diseases including viral, bacterial and parasitic infections.

Many proteins from pathogens share significant sequence or structural similarities with human proteins, and these can also contribute to autoantibody production.

--------------

While the standard of care for chronic inflammatory disease remains the use of medications that slow the immune response, our bodies themselves seek to do the exact opposite; they strive to stimulate the immune system (immunostimulation) when they sense intracellular pathogens.

.....
The answer may lie in the way that pathogens have evolved to slow the defenses of the innate immune system—the very branch of the immune response that would otherwise work to kill them. Indeed, some of these persistent pathogens have long been implicated in autoimmune disease.

------------------------------
VITAMIN D

One of the key mechanisms by which microbes achieve this immunosuppression is by subverting one of the body's most prolific nuclear receptors, the vitamin D receptor (VDR). Defects in VDR signaling transduction have previously been linked to bacterial infection and chronic inflammation.

Defects in VDR signaling transduction have previously been linked to bacterial infection and chronic inflammation.28

This is not surprising as the VDR is responsible for expression of several families of key endogenous antimicrobials, including cathelicidin and the beta-defensins.

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SacredHeart
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Good info. Wish the medical community at large would catch up and stop sticking its head in the sand.

--------------------
Lyme flare June, July, August of 2013. Diagnosed September 2014 Lyme, Bartonella, Mycoplasma, Mono

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WPinVA
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I couldn't get through it all but what I could was extremely interesting.

What did they say to do about it?

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Keebler
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-
Thanks for this article. Thanks very much.

I will need to take some real time to properly read it all.

I've always thought that slapping onto someone with chronic illness the "autoimmune" diagnosis was [very often] a hoax by lazy or judgmental doctors and cover-up so that drugs to manage symptoms would make money

instead of addressing infections that should be treated but get shoved under the carpet.

What to do?

1. Address infection - thoroughly enough, long enough and specifically according to properties of that infection.

This can be done in a variety of ways (not necessarily Rx but also not rule them out) - must be some educated thought that will not accept assumptions and back that up with decisive action, again, for long enough.

2. Support body along the way. Key support is absolutely essential as is reducing / eliminating factors that add stress and deplete chances of success.
-

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Brussels
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Other excerpts, for the ones who cannot read too much (due to brain fog or so):


AUTO IMMUNE is not exactly auto immune (but a response to pathogenic invasion):

Many proteins from pathogens share significant sequence or structural similarities with human proteins, and these can also contribute to autoantibody production.

----------------------
VITAMIN D EXPRESSION (VDR)AND AUTOIMMUNITY

In 2005, Wang et al. demonstrated that the VDR expresses at least 913 genes, many connected to autoimmune conditions and cancers.

Last year a UK-based team used chromatin immunoprecipitation followed by massively parallel DNA sequencing (ChIP-seq) to identify 2776 binding sites for the VDR along the length of the human genome.

Significantly, the binding sites were unusually concentrated near a number of genes associated with susceptibility to autoimmune conditions.

Such genes include IRF8 (multiple sclerosis) and PTPN2 (Crohn's disease and type 1 diabetes).

...................

Key METABOLIC CHANGES within the NUCLEATED CELLS

When microbial ligands dysregulate the VDR, the receptor fails not only to transcribe key antimicrobials but also CYP24A1, a well-studied enzyme which breaks down excess 1,25-dihydroxyvitamin D (1,25-D) into 25-hydroxyvitamin D.

Thus, when activity of the receptor is thwarted, 1,25-D levels rise.

Indeed, Bell has pointed out that a number of infectious diseases—tuberculosis, AIDS with Pneumocystis carinii pneumonia, and AIDS with cytomegalovirus infection, disseminated candidiasis—have high levels of 1,25-D leaking into the bloodstream.

A cross-sectional analysis of 100 patients with autoimmune disease showed that a similar dynamic seems to occur in autoimmune disease.

Confirmation of this observation has been demonstrated in Crohn's disease and rheumatoid arthritis, with Kavathia et al. tying higher levels of 1,25-D to greater disease severity in sarcoidosis patients and Mawer et al. finding that 1,25-D levels were particularly elevated in the synovial fluid surrounding the joints of subjects with rheumatoid arthritis.

(Br: it might be a problem for lyme patients too, in my opinion).

..........

Vit D RECEPTOR AND T3 THYROID HORMONE PROBLEM

We have previously predicted, based on molecular in silico emulation, that at higher concentrations, 1,25-D interferes with expression of several of the body's other key nuclear receptors, including the glucocorticoid receptor, the androgen receptor and the thyroid receptor.

For example, in the case of alpha-thyroid, the agonist T3 would have to compete with the antagonist 1,25-D for access to the receptor ligand-binding pockets.

As the levels of 1,25-D continue to rise, expression of the AmPs by alpha-thyroid would be downregulated.

--------------------------
ABNORMAL VIT D METABOLISM LOWER BODY'S ABILITY TO FIGHT INTRACELLULAR INFECTIONS

Glucocorticoid receptor and androgen receptors would be similarly affected, leading to a profound suppression of the innate immune system's ability to respond to the intracellular attack.

-------------------
PATHOGENS AFFECT VIT D AS A MECHANISM AGAINST THE HOST

Thus, dysregulation of the VDR by pathogenic components of the microbiota could cause flow-on effects that effectively disable the bulk of the body's AmPs, leaving the host increasingly immunocompromised.

The same phenomenon could explain, at least in part, why many autoimmune diseases are characterized by dysregulated hormonal expression—a symptom that often becomes exacerbated as the disease progresses.

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Keebler
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-
Brussels,

Merci Beaucoup! You're a gem.
-

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Brussels
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Another article about Vit D Expression... by pubmed


The Vitamin D Receptor: New Paradigms for the Regulation of Gene Expression by 1,25-Dihydroxyvitamin D3


The actions of the vitamin D hormone 1,25-dihydroxyvitamin D3 (1,25(OH)2D3) are mediated by the vitamin D receptor (VDR),

.... a ligand-activated transcription factor that functions to control gene expression.

Following ligand activation, the VDR binds directly to specific sequences located near promoters and recruits a variety of coregulatory complexes that perform the additional functions required to modify transcriptional output.


Recent advances in transcriptional regulation, which permit the unbiased identification of the regulatory regions of genes, are providing new insight into how genes are regulated.

Surprisingly, gene regulation requires the orchestrated efforts of multiple modular enhancers often located many kilobases upstream, downstream or within the transcription units themselves.

These studies are transforming our understanding of how 1,25(OH)2D3 regulates gene transcription.

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Brussels
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------------------
Brussels: if I understand that well, Vit D3 is a hormone, and is involved in the expression of genes.

Any disfunction in the amount (or quality?) of Vit D3 has influence in our gene expression, meaning, our body will produce different proteins, and it will affect its performance.

The article I posted above says that WHO affects this metabolic problem of D3 are microbes! AIDS, rheum arthritis (lyme included?), tuberculosis, systemic candida, are microbes that influence our metabolism of vit D3.

This is measured by the amount of 1.25D levels in the bloodstream. The more 1.25D is in the blood, the more 'problems' with Vit D3 metabolism you have.

At least, that is how I understood.

The reason microbes affect your Vit D3 metabolism is to downgrade your immune system. Many other hormones in the body will be messed up with that: cortisone, T3 from the thyroid, etc.

I have no doubt that lyme messes up with our hormones (including women hormones, as the whole menstrual cycle gets messed), and also with the T3 (virtually everyone with chronic lyme will have problems there!).

One of the culprits is this bad metabolism of vit D3 caused by microbes!

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Brussels
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CONTINUING, in small parts for people with brain fog:

Fighting inflammation with immunosuppression is NOT the way to go!


.....
Each pathogen that decreases VDR expression makes it easier for other pathogens themselves to slow immune activity even further, creating a snowball effect.

Human genes are up- or downregulated by acquired components of the microbiota, and infected cells progressively struggle to correctly produce human metabolites in the presence of the numerous proteins, enzymes and metabolites generated by the pathogenic genomes.

After a certain level of dysbiosis has occurred, people may well reach the point where they can be diagnosed with an autoimmune/inflammatory condition.

The term ‘inflammaging’ has been coined to explain ‘the now widely accepted phenomenon that aging is accompanied by a low-grade chronic, systemic upregulation of the inflammatory response,

....and that the underlying inflammatory changes are common to most age-associated diseases’.

That many of the pathogens driving the autoimmune disease state may survive by gradually slowing the immune response adds additional weight


....to the contention that immunostimulation rather than immunosuppression is more likely to facilitate reversal of these chronic conditions.

---------------------

Brussels:

what I understood: old age is NOT necessarily linked to increased inflammation, but old age may imply more pathogens, and for that reason, your body gets more and more inflammation as it tries to fight them.

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Brussels
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Further support for successive infection comes from the recent metagenomic studies that show that there does not appear to be a core microbiome across people.

Even among relatively homogeneous populations of fewer than 100 individuals, only a ‘tiny fraction’ of the microbial species inhabiting the gut are shared by other community members.

----------------
Brussels: I find that part of the text very interesting!

We do not have a common microbioma, but all these millions of foreign cells we have are VERY INDIVIDUAL.

No wonder a treatment that works for one has NO EFFECT on a next person!!!

With such a downregulation of the immune system, you got a HOST OF OTHER pathogens (not TICK BORN COINFECTIONS) that will get reactivated.

No single person will have the same pathogen to fight against. It is not only the problem of tick born infections.

I lived that so many times, once my body was taken by infections, tick born infections were just a minor part of the whole problem!

Once all my tick born infections went dormant, I still had loads going on in my body, that has been weakened after decades of immunosuppression (with candida, specially).

Good news: I do feel my Tesla wand solves at least, the Vit D3 problem!!

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Brussels
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HERXHEIMER of intracellular pathogens is HARDER for the body to deal with. No wonder babesia was crazy.

Bart is also intracellular! Candida albicans also.

-----------------
Why is IMUNOSTIMULATION HARDER to the host than IMMUNOSUPPRESSION?


Microbial death leads to the release of toxins and debris into the bloodstream.

The death of intracellular pathogens is particularly difficult for the host to manage, as the body must deal with both the by-products of entire human cells undergoing phagocytosis and apoptosis,

....as well as the microbes that once inhabited them.

In addition, innate immune activity is signaled to the adaptive immune system, initiating the generation of antibodies from the scraps of both cellular and pathogenic debris.

....
In chronic inflammatory disease, the conflict between man and microbe rarely ends.

Perhaps, because chronic microbes appear so effective at progressively and cumulatively slowing the innate immune response, the body ultimately seems unable to reverse the disease state.

What results is a stalemate, where the immune system strives to target the persistent microbes but never fully succeeds, and the initial low-grade inflammation becomes continuous.

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Brussels
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Brussels: When you feel better, you may be sicker than when you feel crap!!! So says the article....

.....

Therefore, once a patient with autoimmune disease has accumulated a high enough microbial load, periods of relief may paradoxically correspond to

....times when the immune system is most compromised, unable to mount an effective immune response against pathogens.

Autoimmune diseases are often characterized by patterns of relapse punctuated by periods of remission.

Indeed, remission may actually signal a kind of exhaustion on the part of the immune system.

On the other hand, relapse, which is often accompanied by a new infection or stress, may represent the immune system's best effort at a response.

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Brussels
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Later in the article, they say:

As previously discussed, microbes including M. tuberculosis, Borrelia and EBV have been shown to downregulate the activity of the VDR.

As expression of CYP24A1 diminishes, 1,25-D levels rise.

When the hormone/secosteroid rises above a normal range, it may downregulate, via the nuclear receptor pregnane X receptor, the amount of pre-vitamin D converted into 25-D.38 The result is that 25-D levels drop.

---------------
So yep, Borrelia downregulates VDR, makes you lose 25-d, and before that, the author recommends supplementation of Vit D3 (even in great amounts).

Another suggestion is giving Olmesartan to patients to regulate this Vit D3 metabolism...

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Brussels
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The article goes on, saying that supplementing with Vit D will be immunosuppressive, not stimulant, and make the immune system problem go worse.

Their suggestion is to use a drug that is a VDR agonist, olmesartan medoxomil. With that drug, they say they are able to reactivate the immune system.

They use antibiotics together with Olmesartan with amazing results for different immunosuppressed patients.

It takes though time, not a fast treatment, patient goes through innumerous herxheimer reactions. And patient uses abx together with Olmesartan (it is a hypotensive drug).

------------------------------
Article:
It may seem unrealistic that a VDR agonist could cause what appears to be immunopathology, let alone eventual improvement in patients with so widely differing disease states.

Yet, we have been collecting many reports of improvement of patients with a wide range of autoimmune and inflammatory conditions.


The antimicrobial peptides activated by the therapy are able to target vastly different pathogens under very different circumstances.

Some even have activity against certain species of antibiotic-resistant bacteria.

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Brussels
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Abx usually do not work if patient is immunocompromised:


Antibiotics may be generally ineffective at generating immunopathology if a patient is immunocompromised.

Under these conditions, the immune system may not be able to potentiate the actions of the antibiotics in a manner that would allow them to generate significant microbial die-off.

The following case history illustrates how, when certain subinhibitory antibiotics are taken in conjunction with the immunostimulant olmesartan, patients generally become much more sensitive to these antibiotics.
----------

Brussels: the article goes on saying that abx will work better, if the immune system is reactivated with Olmesartan.

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delljen
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Brussels,

This is all very fascinating, thank you.

Question about this statement; "Their suggestion is to use a drug that is a VDR agonist, olmesartan medoxomil. With that drug, they say they are able to reactivate the immune system."

I think that Curcumin has also been discussed in scientific literature as being a VDR agonist. Could the use of say, Lipsomal Curcumin, act in a similar way as the drug, Olmesartan Medoxomil in reactivating the immune system?

Or am I way off?

"Stimulation of VDR by curcumin might shift this balance to the inhibitory activity of VDR." (Kewitz)

Kewitz :
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3941149/

Also this on, Immunomodulatory effects of curcumin: in-vivo.
http://www.ncbi.nlm.nih.gov/pubmed/18387511

Thanks again!

--------------------
Lyme, Bart, Babs D, FL1953
I am just sharing my thoughts and experiences - I'm not a medical professional.

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Carmen
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thanks Brussels for bringing this topic up.

I have long known these FACTS. I learned them from naturopathic doctors in the 80s. Dr. Donsbach being one of the leading educators on the concept that RA is a reaction to a microbial invasion and because of this understanding he has been very successful in treating advanced cases of RA through diet, cleanses, parasite cleanses, and natural antimicrobials as well as supplements that support and balance the immune system, as well as bee sting therapy.

Autoimmune system diseases like RA, ALS, Sjogren's disease, Lupus, MS and so many others are merely BASKET DIAGNOSIS. Throwing a bunch of symptoms into a basket, giving it a name and not knowing the etiology.

The medical system seems to have largely divorced itself from etiology these days. Why? Because etiology brings you to the truth and conventional medicine cannot deal with the truth for it interferes with its paradigm of monetary rape of the public.

If one wanted to deal with truth one would not use antibiotics the way they do, nor steroids, nor vaccines.

They are about to set up a killing field in California with mandatory vaccines for all children, no exceptions. There are bills being prepared for mandatory vaccines for adults there too. Vaccines truly damage the immune system so pathogens can run wild in some people who cant handle it.

And this is why the dark field live blood analysis is not permitted for medical doctors. Medical doctors are not even permitted to have any kind of microscope in there office in some states... or just for very limited use. God forbid anyone might see the truth.

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rowingmom
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Good overview. Thanks very much.

What you are describing (abx along with olmesartan (Benicar)) is the Marshall protocol. However, it also requires that you completely avoid vitamin D, which I am not prepared to do. I think sunlight is too important to avoid.

I have been reading about GcMAF lately because several US doctors associated with it's use have either disappeared or died.

http://www.naturalnews.com/050582_nagalase_GcMAF_cancer_industry_profits.html

http://www.naturalnews.com/050553_Dr_Bradstreet_GcMAF_cancer_therapy.html

http://www.naturalhealth365.com/cancer_treatments/gcmaf_protein.html

"GcMAF (Gc Macrophage Activating Factor) is a natural protein that all healthy people naturally have inside of them. It is an immune system modulator that works by stimulating the activity of macrophages – the “big eaters” of our immune system. But, a negative influence on GcMAF is nagalase – an extracellular matrix-degrading enzyme that is secreted by cancerous cells in the process of tumor invasion.

When nagalase levels are elevated, it affects the levels of GcMAF – potentially disrupting the activation of macrophages that protect us from disease.

Since viruses and diseased cells release negalase, people who have a higher level of nagalase, will ineffectively deal with immune system invaders. Children with learning disorders to cancer patients typically have elevated nagalase levels – sometimes by as much as three times the normal level.

Researchers and practitioners have demonstrated that GcMAF can reverse diseases that attack the immune system such as: chronic inflammation, bacterial and viral infections, chronic herpes, chronic acne, Lyme disease, fibromyalgia osteoporosis, Hodgkin’s, Lupus, MS, Parkinson’s and remarkably – autism."

I completely agree with you that autoimmune responses can be caused by infectious organisms. The first time I saw mention of this was in Buhner's Mycoplasma and Bartonella coinfections book.

Before treatment K had positive ANA (Antinuclear Antibodies) titers, with bartonella treatment they resolved.

--------------------
13 yo DX PANS/Tourette's/Asperger's/ADHD treated for Igenex positive bartonella/IND lyme with 2 years of abx treatment. Weaned off abx April 2013 at 80% improvement. Continuing with Buhner bartonella/babesia protocols. Aug 2014 99% improvement.

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Brussels
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Thanks for comments!

Yep, this sounds like Marshal protocol.

I did supplement with D3 the whole time I had lyme and felt better. Even after lyme.

Dr. K. says that the Marshal protocol works for people with lyme and sarcoidosis, but not for most chronic lyme patients.

---------------

I just posted this article because I got it from someone who studies longitudinal waves.... But I thought it got some interesting concepts, that I also had heard through dr. K.

And as I can test people energetically, I swear that everyone with arthritic problems (almost everyone) will test for active pathogens in the joints. If not testing today, it will test in another occasion.

I also posted that because some people in this forum post about 'from chronic lyme to auto immune" as though both were 'different' diseases!

The point is that they are not different, but cousins (and possibly just not 2 diseases, but just one immunologic disease, as stated in the article).

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Brussels
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Carmen is very right, unfortunately.

So sad that compulsory vaccinations are starting.

History shows that when a minority imposes too damaging (and life threatening) measures to the majority, the majority reacts and put the minority out.

Let's see what history will show. You all stay quiet, obedient, accepting what is imposed, well, your health will get damaged.

---------------

As for turmeric /curcumin, thank you so much for the interesting article!

It's a reminder of how much simple spices can be healing.

I guess you are right, it is a VDR agonist.

I wonder why I couldn't take turmeric while sick with lyme (it caused me terrible stomach aches). Even at very MINUTE amounts.

You bet I tried to take it!

Other Indian spices, that have been less studied, I could take it. One that I swear that acts as antimicrobial, anti babesial, anti lyme cysts is cardamon.

I never saw anything published about cardamon, but since I started using it, it tested so many times as antimicrobial, that i take it almost EVERY DAY, ever since I started (in my coffee, tea, most dishes I cook).

Just one naturopath I know, who tests people energetically adopted my idea, but she said it tested very good to many people with lyme too!

I had added turmeric slowly to my rice recently, without adverse reactions, so far. I will try it again, more systematically.

Thanks for the interesting publication on curcumin!!

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