LDI: A PROMISING TREATMENT FOR LYME AND ME/CFS

[serg1942]

LOW DOSE IMMUNOTHERAPY (LDI):
A PROMISING TREATMENT FOR CHRONIC LYME DISEASE AND ME/CFS

Download article by clicking here

Hi everybody,

I would like to share with you an article about the therapy LDI (Low Dose Immunotherapy), I have been working on for a couple of months. Last year in medical school, I had the opportunity to see how well the specific-allergen-based-immunotherapy (AIT) worked for certain allergies, and then I thought it would not be so inconceivable to do something similar with a chronic infection. Much to my surprise, a couple of months later, @Sushi talked me about LDI, and because I already knew the mechanisms underlying the conventional immunotherapy for allergies, I started to review some of the available literature on other forms of immunotherapy. Interestingly--and frankly very striking--I found a great deal of peer-review studies showing successful results for a variety of autoimmune conditions and chronic infections. Then I decided to investigate whether these versions of the conventional antigen-based-immunotherapy (i.e., LDA/LDI) could be of any help for either chronic Lyme disease or ME/CFS.

The result of this study is the article I am attaching. Although it is not as thorough as I would've liked to (I would have needed 6 months more to finish it up properly), I think it contains enough evidence to support the conclusions I have finally reached--which you can find in the article.

On the other hand, I have written it in English, but as you can notice, it is not my first language, so I apologize for the grammar mistakes it sure contains. I just hope it is understandable enough. If you read it and find a phrase you cannot understand because of improper grammatical construction, wrong vocabulary, etc., I would really appreciate you would let me know, so I can change it and thus help other fellows who might want to read it as well (ideally with the proposed correction).

Finally, I am sorry it is not written in a proper format for many ME/CFS or Lyme fellows because of the cognitive issues... The long paragraphs and the text in bold--and even worse the text both in bold and underlined!!--can be difficult for many (I used a format I know will be easier for some Spanish doctors to whom I want to forward the text). Also, the text is quite technical; while initially I started explaining the basic science in order to understand the whole text, I realized it was an endless task, especially in English... So, because I do have to start focusing on the current university year (that has started already and need to "catch up" with as much as I am able to--as I start the hospital practices next week and have not opened a book yet!), this is all I have been able to do (have not even translated it into Spanish... and I feel so bad about!).

Despite all this, I do hope it is helpful, and most importantly, I hope the theoretical potential LDI seems to bear, actually gets translated into practical terms.

Best!
Sergio

 

[Helen]

As I already had access to your article I just want to say thank you so much, Sergio, for doing such great job writing this introduction, also with references. It is a lot to digest, but very interesting

 

[justy]

This looks great - thank you Sergio for all your hard work!

I am sadly unable to read much at the moment due to worsening of my health after trying gamma globulin injections.
Nevertheless i am interested and will attempt t read some of it a little bit at a time.

Have you had or are you planning to have LDI for Lyme and chronic infections?

secondly my major concern, and one I have been unable to find much about, is around the issue of LDI when the patient has developed Mast Cell Activation Disease secondary to issues such as Lyme, mold etc.

How I understand it is that MCAD's are not true allergies and that far from alleviating the problem of aberrant mast cell degranulation etc EPD, LDA and possibly LDI could add to the problem for these patients. I have been told to avoid anything that triggers my mast cells to degranulate in the hope that they will eventually 'quieten down'. Of course they are unlikely to fully 'quieten down' until the underlying triggering event eg Lyme mold etc is removed, leading to the catch 22 that patients with infections And MCAD's can't tolerate treatments, but cant get better from the MCAD's until they treat the infections.

I would really like to find out about the safety and mechanism of action of LDI in people with MCAD's, but can find no information on the situation anywhere.

I was offered Low DOse Immunotherapy by the Breakspear clinic for what they termed my 'allergies' I then found out that I didn't have allergies but MCAD, therefore receiving desensitisation could have put me at great risk of anaphylactic shock or other issues from prompting degranulation or histamine build up.

 

[Jon_Tradicionali]

I'll go through it tonight Sergio.

I've seen a few studies recommending immunotherapia as an effective treatment for CFS but always hit a roadblock whenever I researched the term and its proposed function/purpose.

 

[Sushi]

Great job, @serg1942 ! This was a paper that needed to be written and even though you couldn't devote as much time to it as you wished, I think you have made a very good contribution to the information available.

 

[serg1942]

Hi @justy,

I am flying to BXL to see Dr. KDM within a few hours, so I'll get back to you at the end of the week when I am back.

Just a quick note: as far as I understand it, LDI should actually reduce Mast Cell Activation Disease, because it raises IL-10, which in turn changes the threshold of activation of mast cells, and also reduces the content of their granules (such as histamine). Furthermore, LDI stimulates the production of IgG4, that further prevents the activation of basophils and mast cells by competition with IgEs. Moreover, LDI also deviates the formation of IgEs toward the IgG4, what will further lower mast cells degranulation...

Hugs!!!
Sergio

 

[Bansaw]

Hi @justy,

Thanks Sergio. I may be getting some LDA Immunotherapy because I have a dust mite allergy.
I must admit I lack the endurance to wade through your paper. Could anyone explain to me in real simple laymans terms how this works? I know the concept of LDA allergy treatment, - you get a minor dose of the allergen and it prompts your immune system to respond correctly. But , how does this work for CFS?

 

[serg1942]

Hi @Bansaw, it actually works the same way immunotherapy does for allergy. Even though it has not yet proved a trigger agent causative of the immune profile of ME/CFS: [chronic immune activation (anti-inflammatory phenotypes of Th2 and Th17, polyclonal B cells activation, autoreactive B and T cells...) + chronic systemic inflammation (PGE2, IL-8, IL-1, IL6, MCP-1...) + chronic immune suppression (suppressed Th1, low NKs,low CD8+ citotoxic cells and activity...) + autoimmune processes ], this is a response expected from chronic intracelullar infections. In this vein, in ME/CFS, there is plenty of evidence about chronic herpes virus, but also about "master infections" such as borrelia, bartonella, babesia.. (For these the peer review literature is very limited but the empiric evidence seems to be huge and growing). So, the idea is to treat those infections with LDI, as it is done in allergy with the antigens that cause the pathological reaction.

Thing is, most ME/CFS are positive for Lyme disease (Borrelia b), which is known to be a master infection. The reactivation of EBV, CMV, and other herpes viruses is also a fact. So, even in the worse scenario in which the true first trigger has not been found yet, by treating the infections we have, it would be logical to expect some benefit... A best scenario would be that these intracelullar infections, which are known to induce the exact immune profile of ME/CFS, and which have shown to be in most patients, are in fact the initial triggers...what would mean LDI could have a healing potential. Time will tell of course (not to forget mold or chemicals that can be also treated with LDI).

Finally, and what I like the most, is the "bystander suppression" phenomenon LDI can induce, which means that even if you don't treat the "true-first-trigger", by treating a pathogen or a chemical that might very well be in the vicinity of this first-trigger, you would be actually switching off an improper response towards the real trigger as well (because the cytokines released to create the immune tolerance you want to, are non-specific, and thereby will act on any antigen that is closeby, if your immune system is reacting in a wrong way towards it).

Hope I have made it easier to understand!

Best!
Sergio

 

[Bansaw]

Hope I have made it easier to understand!
Best!
Sergio

I read somewhere that a majority of people have the herpes virus. And, I don't think I have Lymes, but I was tested positive for Rickettsia Mooseri (Endemic Typhus) for which I took a punishing course of antibiotics.
Did you mention that you were seeing Dr.Merlier ? I am praying for a door to open to see him in a few months. We'll see...
I am assuming the LDI will be different for each individual based on what ailments they have?
Thanks so much for your work on this. Please keep us up to date as you find things out. : )

 

[ScottTriGuy]

@serg1942

Hi Sergio,

How are you feeling about your meeting with KDM and subsequent treatment protocol (if any)?

Would HIV infection be an example of a 'master infection'?

thanks,
Scott

 

[Gingergrrl]

secondly my major concern, and one I have been unable to find much about, is around the issue of LDI when the patient has developed Mast Cell Activation Disease secondary to issues such as Lyme, mold etc.

@justy, all of your questions are identical to mine re: the safety of LDI when a person also has MCAD/MCAS, mastocytosis or any mast cell disease. For me the trigger of the MCAS was severe toxic mold exposure vs. Lyme but in both cases, I cannot find anything that explains if LDI is really safe with MCAS and it may be that the answer is just not known yet.

How I understand it is that MCAD's are not true allergies and that far from alleviating the problem of aberrant mast cell degranulation etc EPD, LDA and possibly LDI could add to the problem for these patients. I have been told to avoid anything that triggers my mast cells to degranulate in the hope that they will eventually 'quieten down'. Of course they are unlikely to fully 'quieten down' until the underlying triggering event eg Lyme mold etc is removed, leading to the catch 22 that patients with infections And MCAD's can't tolerate treatments, but cant get better from the MCAD's until they treat the infections.

Agreed they are not true IgE mediated allergies and if the LDI caused mast cell degranulation it could be dangerous IMO. (Not necessarily any more dangerous than any other med or supplement and every new thing I try now, there is that risk once you have MCAS.)

I would really like to find out about the safety and mechanism of action of LDI in people with MCAD's, but can find no information on the situation anywhere.

I couldn't find any either but would love to read it if you or anyone does. Am doing a different mold protocol and would not try LDI at present anyway but am curious for the future.

I was offered Low Dose Immunotherapy by the Breakspear clinic for what they termed my 'allergies' I then found out that I didn't have allergies but MCAD, therefore receiving desensitisation could have put me at great risk of anaphylactic shock or other issues from prompting degranulation or histamine build up.

Do you think it's possible what they offered you at Breakspear was different than the current LDI? But I agree if Breakspear didn't know you had MCAS, they could have put you at risk for ANA. And from your earlier post, it is a huge catch 22 issue for me too that many potential treatments that could help me, I cannot tolerate b/c of the MCAS.

 

[Sushi]

I cannot find anything that explains if LDI is really safe with MCAS and it may be that the answer is just not known yet.

I know one patient with extremely severe MCAS who has not reacted to the first dose.

I couldn't find any either but would love to read it if you or anyone does. Am doing a different mold protocol and would not try LDI at present anyway but am curious for the future.

There are quite a few mold patients doing LDI. When I remember to note their results I'll post them.

Do you think it's possible what they offered you at Breakspear was different than the current LDI?

Yes, it is different. LDI has only been given for about 2 years and never at Breakspear.

 

[Daffodil]

@serg1942 ...hi serg. i wonder if you might give an opinion about why most people who carry Lyme infections do not get CFS. do you think that those who got sick after "mono" were weakened enough that the Lyme bacteria happened to spread and no longer remained latent?

Also, do you have any opinion on the study that showed spinal fluid of Lyme patients to have a different protein profile than those with CFS? If lyme is the master infection in CFS, why would the proteins of the two patient populations be distinct?

thank you!!

 

[serg1942]

Hi @Daffodil,

I'll have to be brief, as I am in the middle of exams (I'll check on the forum in 4 weeks from now, when I finish, and will reply longer if you have further questions that I can help with, or in order to reply to your opinions, ok?. As for the first question, it is my understanding that the results of a research are going to come up very soon, explaining why some people fall sick with Lyme and some don't. My guess is that is has to be with polymorphisms at the very root of the interaction bacteria-immune system, this is, probably related with the innate system. So I think there might be 2 clusters, the ones who will never be able to be affected by Bb and the ones who might. As for the later, well, of course, this is only speculation at this point, but I think they could be able to carry the infection "latent", and as you say, we might requiere a acute or chronic event that directly/indirectly lowers the immunity (again, probably the innate, and I'd bet at the gut) in order for the bacteria to infect us.

However I don't know whether it is only Bb the only pathogen that can cause ME/CFS. What seems clear to me and it is very well documented, although not yet properly compiled is that ME/CFS is caused in most people by something that inhibits the Th1 and the Th17 responses at the same time that creates a antiinflammatory Th2 deviation and a chronic systemic inflammation--that in turn favors autoimmune processes-- Well, this pattern, to my knowledge, is shown by some intracelullar infections which get chronic (it is the only way the can actually do it, and the mechanism is quite standard), as well as by malignant cells (but these cannot get chronic by definition...). This pattern is also found in many systemic autoimmune conditions, and there is growing evidence on the role of intracelular pathogens linked or directly being the direct cause of these diseases (e.g. Crohn, RA, or ankylosing spondylitis). So it seems clear to me that ME/CFS must be caused by intracelullar pathogens able to get chronic by inducing this immune pattern. Only Bb? Well, there is not evidence to draw solid conclusions here, but it seems to be the experience of many cutting edge doctors on ME/CFS that Bb is active is most ME/CFS patients.

So, finally, and regarding your second question, I wrote about it time ago--not sure if I added this part to the article on LDI... Anyway, let me paste it below. As you can see, it is my layman's opinion that they actually demonstrated the oposite of what they explained. Hope it helps!!

Best!
Sergio


"(...)"There are some studies on the other hand suggesting these two similar diseases to be different entities. Probably the most illustrative work in this field was performed by Schutzer et al. (2011). They used liquid chromatography coupled to high-resolution mass spectrometry based label-free quantitative proteomics approach to examine cerebral spinal fluid (CSF) samples from patients with CFS/ME, Lyme disease and healthy controls, and were able to distinguish either of each group from the others based on their unique CSF proteins [While the authors conclude that this findings suggest a different etiology of both conditions, it is my personal opinion that these results did not have important factors into account when achieving such conclussion. As it has been clearly stated by numerous papers, ME/CFS is not a statistic disease, i.e. its pathophysiology varies both over time as well as according to the degree of symptoms severity. This distinction was not made in this study. In adittion, the diagnosis criteria for CFS was not the proper international ones such as, the Canadian Consensus or the International Consensus criteria. Rather, patients were selected by experts in fatigue and pain disorders, and also underwent psychiatric analysis and several blood tests to rule out common causes of fatigue, however the post-exertional malaise, an international hallmark of ME/CFS diagnosis, was not taking into account. Also, a positive result for Borrelia b. infection was included between the excluding factors for selecting the CFS patients; this might have biased the results, given that the aetiology of ME/CFS is unknown, and infections--including Bb.-- are considered to play a pivotal role in etiopathogenesis of the disease; therefore the CFS group was not representative of the whole ME/CFS community who would fall under the International criteria. Moreover, the patients included in the Lyme disease group had to fit the CDC criteria, that according to international organizations and physicians all over the world, might miss most patients with chronic Lyme disease. Even more, all LD patients were seropositive for antibodies to Bb. As previously reviewed, Lyme patients normally loss the capacity of generating detectable isotypes and amounts of antibodies, so patients with a preserved a proper anti-humoral response towards Bb., are by no means representative of the whole chronic LD patients community, and rather, they seem could represent only the small percentage who still have a strong Th2 response towards the bacteria--which is usually lost over time. Finally, out of the 2768 measured proteins, the authors highlight 4 proteins related with complement activation (C1S, C4B, C1QB, C1QC) which were differentially increased in abundance consistently across the LD patients compared to CFS patients. The authors expose this difference as suggestive of possible different pathogenic mechanism (I have earlier discussed how different strains of Bb and different immune hosts responses were responsible for different degrees of complement activation by the bacteria). In this regard, the fact that the complement cascade is activated in both conditions, could on the contrary indicate similar underlying mechanism, while the higher activation observed in the LD patients could fit with a subset of LD patients with a preserved innate response. The same could apply to the proteins found to be decreased in both CFS and LD patients compared to healthy normal controls some of which were related to networks relevant to neurological function. They found the CFS group to a more pronounce decrease; this again would support my previous reasoning. In conclusion, it is my opinion that the results of this study, far from demonstrating a clear distinction between CFS and chronic LD, they could be showing the same condition throughout different stages, versus healthy controls]. (...)".


Schutzer SE, Angel TE, Liu T, Schepmoes, AA, et al. Distinct cerebrospinal fluid proteomes differentiate post-treatment lyme disease from chronic fatigue syndrome. PLoS One. 2011; 6 (2): e17287.

 

[ahmo]

What seems clear to me and it is very well documented, although not yet properly compiled is that ME/CFS is caused in most people by something that inhibits the Th1 and the Th17 responses at the same time that creates a antiinflammatory Th2 deviation and a chronic systemic inflammation--that in turn favors autoimmune processes--

Low dose naltrexone (LDN) made a significant difference for me, presumably acting on this system.

Thanks for your work and Good luck w/ your exams.

 

[jimmy86]

Interesting hypothesis. I started with allergy immunotherapy against bees the year before I got CFS/ME. In retrospective I always thought this did more harm than good and messed up my immune system...

 

[serg1942]

Hi @jimmy86 , thank you. I'll be starting myself this treatment on Wednesday, so, I will for sure let you now how it works. However I would like to say that it is no longer a theory. The level of evidence is C or III (expert opinions), as some doctors are sharing their successful experience on treating ME/CFS with LDI. But,of course, it is still too early to draw any general conclusion.

On the other hand, I did extrapolate the results of antigen-specific-based-immunotherapy to ME/CFS from research made on autoimmune diseases and on intracelular chronic infections. This is indeed a theory. However it is not a theory the fact that the evidence makes it very clear that ME/CFS's symptoms are directly caused by inflammation that favors in turn autoimmunity, and that the immune profile shown by ME/CFS patients is that of a chronic intracelular infections. And these 3 facts are shared by all the conditions for which this kind of immunotherapy has proven to be of benefit.

With the above said, I must say I am very cautious, so I will just try it and see if my extrapolation, which coincides with the level of evidence C, turns out to be true at the end. It is not an easy treatment to prescribe or follow, and as of today there are very few doctors really prepared to do it properly...

As for your experience, I think it makes perfect sense. Normally it is needed a trigger to fall sick, and a high dose of an allergen you are overreacting to, seems to me like the perfect one... On the other hand it is further proof about the power of antigen-based immunotherapy to "hit" your immune system, in one or another direction...

Best!
Sergio



Well, thank god I know about the

 

[roller]

what then to take?

just homoeopathic allergenes (= anti-allergy meds) ?

 

[Thinktank]

@serg1942 , have you started the LDI treatment? How's it going?

 

[Sushi]

@serg1942 , have you started the LDI treatment? How's it going?

Can't speak for Sergio but it is going well for me. Not ready to post details yet, but so far very encouraging.